PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 32383521-2 2020 Insulin signaling is initiated by the phosphorylation of insulin receptor substrate-1 (IRS-1) at tyrosine (pTyr) residue. Tyrosine 97-105 insulin receptor substrate 1 Homo sapiens 57-85 33927970-3 2021 In recent years, a growing number of studies has documented that dysregulation of insulin signaling is a key feature of AD and has crucial correlations with serine/tyrosine (Ser/Tyr) phosphorylation of insulin receptor substance-1(IRS-1). Tyrosine 164-172 insulin receptor substrate 1 Homo sapiens 231-236 32798372-4 2021 The insulin signalling is controlled through tyrosine phosphorylation of IRS-1 and IRS2, and dysregulation of IRS proteins signalling may lead to glucose intolerance and eventually insulin resistance. Tyrosine 45-53 insulin receptor substrate 1 Homo sapiens 73-78 32383521-2 2020 Insulin signaling is initiated by the phosphorylation of insulin receptor substrate-1 (IRS-1) at tyrosine (pTyr) residue. Tyrosine 97-105 insulin receptor substrate 1 Homo sapiens 87-92 32337956-9 2020 Its overexpression also increased Grb2 expression and phosphorylation of AKT1 through elevation of IRS1 tyrosine phosphorylation in IRS1-transfected U-87 MG cells compared to control and mock transfected groups. Tyrosine 104-112 insulin receptor substrate 1 Homo sapiens 99-103 32337956-9 2020 Its overexpression also increased Grb2 expression and phosphorylation of AKT1 through elevation of IRS1 tyrosine phosphorylation in IRS1-transfected U-87 MG cells compared to control and mock transfected groups. Tyrosine 104-112 insulin receptor substrate 1 Homo sapiens 132-136 32010350-2 2019 IRS-1 Gly971Arg polymorphism can modify tyrosine phosphorylation at a specific site of IRS-1 and may have a critical role in the development of insulin resistance (IR). Tyrosine 40-48 insulin receptor substrate 1 Homo sapiens 0-5 31539648-3 2019 Insulin-evoked insulin receptor (IR) activation increases activated, tyrosine-phosphorylated IRbeta on tyrosine residues 960, 1150, and 1151, insulin receptor substrate-1 recruitment to IRbeta and phosphorylated RAC-alpha-serine/threonine-protein kinase. Tyrosine 69-77 insulin receptor substrate 1 Homo sapiens 142-170 31539648-3 2019 Insulin-evoked insulin receptor (IR) activation increases activated, tyrosine-phosphorylated IRbeta on tyrosine residues 960, 1150, and 1151, insulin receptor substrate-1 recruitment to IRbeta and phosphorylated RAC-alpha-serine/threonine-protein kinase. Tyrosine 103-111 insulin receptor substrate 1 Homo sapiens 142-170 32010350-2 2019 IRS-1 Gly971Arg polymorphism can modify tyrosine phosphorylation at a specific site of IRS-1 and may have a critical role in the development of insulin resistance (IR). Tyrosine 40-48 insulin receptor substrate 1 Homo sapiens 87-92 30928401-8 2019 In addition, didymin activated insulin receptor substrate (IRS)-1 by increasing phosphorylation at tyrosine 895 and enhanced the phosphorylations of phosphoinositide 3-kinase (PI3K), Akt, and glycogen synthasekinase-3(GSK-3). Tyrosine 99-107 insulin receptor substrate 1 Homo sapiens 31-65 29526746-7 2018 In addition, the classical tyrosine phosphorylation response of insulin was reduced by NaAsO2, as evidenced by reduction of insulin-induced tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate-1(IRS-1). Tyrosine 27-35 insulin receptor substrate 1 Homo sapiens 223-228 32422022-3 2019 Upon binding of the insulin and insulin-like growth factor-1 (IGF-1), IR is activated by increasing the levels of tyrosine-phosphorylated (pY) IRP on tyrosine 960, 1150, and 1151 residues as well as IRS-1 recruitment to IRbeta. Tyrosine 114-122 insulin receptor substrate 1 Homo sapiens 199-204 30052036-7 2018 HucMSC-ex restored the phosphorylation (tyrosine site) of the insulin receptor substrate 1 and protein kinase B in T2DM, promoted expression and membrane translocation of glucose transporter 4 in muscle, and increased storage of glycogen in the liver to maintain glucose homeostasis. Tyrosine 40-48 insulin receptor substrate 1 Homo sapiens 62-90 30138966-8 2018 (3) Adiponectin induces increased tyrosine phosphorylation of IRS1 in a time-and concentration-dependent manner. Tyrosine 34-42 insulin receptor substrate 1 Homo sapiens 62-66 30640362-7 2019 Main Outcomes and Measures: The main outcome was augmented brain insulin signaling that manifested as a change in tyrosine phosphorylated insulin receptor substrate 1 within neuronal extracellular vesicles at the end of 48 weeks of exenatide treatment. Tyrosine 114-122 insulin receptor substrate 1 Homo sapiens 138-166 30640362-10 2019 Patients treated with exenatide had augmented tyrosine phosphorylation of insulin receptor substrate 1 at 48 weeks (0.27 absorbance units [AU]; 95% CI, 0.09-0.44 AU; P = .003) and 60 weeks (0.23 AU; 95% CI, 0.05-0.41 AU; P = .01) compared with patients receiving placebo. Tyrosine 46-54 insulin receptor substrate 1 Homo sapiens 74-102 29769704-7 2018 RESULTS: PCA restored insulin-induced phosphorylation in OB-VAT by increasing phospho-Tyr-IRS-1 and phospho-Ser-Akt after insulin stimulation as observed in NW-VAT (p < 0.05). Tyrosine 86-89 insulin receptor substrate 1 Homo sapiens 90-95 30092354-1 2018 Regulation of tyrosine phosphorylation on insulin receptor substrate-1 (IRS-1) is essential for insulin signaling. Tyrosine 14-22 insulin receptor substrate 1 Homo sapiens 42-70 30092354-1 2018 Regulation of tyrosine phosphorylation on insulin receptor substrate-1 (IRS-1) is essential for insulin signaling. Tyrosine 14-22 insulin receptor substrate 1 Homo sapiens 72-77 30381640-4 2018 First, we determined that atorvastatin inhibits the tyrosine phosphorylation of insulin receptor substrate (IRS)-1 through a decrease in the RhoA-Rho-kinase pathway, resulting in the inhibition of glucose uptake. Tyrosine 52-60 insulin receptor substrate 1 Homo sapiens 80-114 29679000-8 2018 Regardless of the experimental method (in vivo or in vitro), tyrosine phosphorylation of IRS-1 and Akt were significantly lower (P<0.01) and serine phosphorylation was significantly higher (P<0.01) in the model group than in the sham/control group. Tyrosine 61-69 insulin receptor substrate 1 Homo sapiens 89-94 29233661-4 2018 We found that FYGL inhibited overexpression of PTP1B in liver tissues of ob/ob mice and HepG2 cells, significantly improved the phosphorylation of IRS1 on tyrosine residues, activated phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt) cascades and increased phosphorylation of glycogen synthesis kinase-3beta (GSK3beta), finally enhanced insulin-stimulated glycogen synthesis in HepG2 cells and decreased blood glucose in insulin resistance model mice. Tyrosine 155-163 insulin receptor substrate 1 Homo sapiens 147-151 29393871-5 2018 In addition, they stimulated the phosphorylation levels of the components of the insulin signaling pathway, including tyrosine phosphorylation of IRS-1, and serine phosphorylation of Akt and GSK-3beta. Tyrosine 118-126 insulin receptor substrate 1 Homo sapiens 146-151 30381640-5 2018 Second, we found that TNF-alpha induces IRS-1 phosphorylation at serine residues 636/639 and inhibits the tyrosine phosphorylation of IRS-1 through the increase in both extracellular signal-regulated kinase (ERK) and c-jun N-terminal kinase (JNK) phosphorylation. Tyrosine 106-114 insulin receptor substrate 1 Homo sapiens 134-139 28869341-6 2017 EGCG also alleviates insulin resistance by enhancing tyrosine phosphorylated levels of IRS-1, stimulating the translocation of GLUT2, and activating PI3K/AKT as well as AMPK signaling pathways in a Bmal1-dependent manner both in HepG2 cells and primary hepatocytes. Tyrosine 53-61 insulin receptor substrate 1 Homo sapiens 87-92 29027136-6 2017 In addition, oligonol activated insulin receptor substrate 1 by reducing phosphorylation at serine 307 and increasing that at tyrosine 895, and enhanced the phosphorylations of Akt and phosphatidylinositol 3-kinase. Tyrosine 126-134 insulin receptor substrate 1 Homo sapiens 32-60 28082684-1 2017 Insulin binds to the insulin receptor (IR) and induces tyrosine phosphorylation of the receptor and insulin receptor substrate-1 (IRS-1), leading to activation of the PKB/Akt and MAPK/ERK pathways. Tyrosine 55-63 insulin receptor substrate 1 Homo sapiens 100-128 28460125-6 2017 Treatment of GCs with FSH and exogenous IGF-1 initiates synergistic IRS1 Tyr phosphorylation and resulting gene activation. Tyrosine 73-76 insulin receptor substrate 1 Homo sapiens 68-72 28011403-6 2017 We observed that these effects were exerted by changes on the phosphorylation of IRS-1 on specific serine and tyrosine residues modulated by PA through the modulation of JNK and IKK activity. Tyrosine 110-118 insulin receptor substrate 1 Homo sapiens 81-86 28082684-1 2017 Insulin binds to the insulin receptor (IR) and induces tyrosine phosphorylation of the receptor and insulin receptor substrate-1 (IRS-1), leading to activation of the PKB/Akt and MAPK/ERK pathways. Tyrosine 55-63 insulin receptor substrate 1 Homo sapiens 130-135 27434075-6 2016 IRS-1 phosphorylation of HG-treated podocytes was negatively regulated, favoring serine versus tyrosine residues. Tyrosine 95-103 insulin receptor substrate 1 Homo sapiens 0-5 26702053-3 2016 We have used ovarian granulosa cells as a model to investigate this pathway, based on evidence that the GPCR agonist follicle-stimulating hormone (FSH) promotes the protein kinase A (PKA)-dependent phosphorylation of insulin receptor substrate 1 (IRS1) on tyrosine residues that activate PI3K. Tyrosine 256-264 insulin receptor substrate 1 Homo sapiens 217-245 26702053-7 2016 Activation of PI3K thus requires both PKA-mediated relief of IRS1 inhibition and IGF-1R-dependent tyrosine phosphorylation of IRS1. Tyrosine 98-106 insulin receptor substrate 1 Homo sapiens 126-130 26702053-8 2016 Treatment with FSH and increasing concentrations of exogenous IGF-1 triggers synergistic IRS1 tyrosine phosphorylation at PI3K-activating residues that persists downstream through protein kinase B (AKT) and FOXO1 (forkhead box protein O1) to drive synergistic expression of genes that underlies follicle maturation. Tyrosine 94-102 insulin receptor substrate 1 Homo sapiens 89-93 25667086-6 2015 Insulin receptor substrate-1 (IRS-1) is recruited to interact with the IR-catalyzed phospho-tyrosine cav-2, which facilitates IRS-1 association with and activation by IR to initiate IRS-1-mediated downstream signaling. Tyrosine 92-100 insulin receptor substrate 1 Homo sapiens 0-28 26950447-2 2016 IRS1 is the best studied member of this family and insulin-induced Tyrosine phosphorylation of (YXXM) motifs provides docking site for SH2 domain-containing proteins. Tyrosine 67-75 insulin receptor substrate 1 Homo sapiens 0-4 26950447-7 2016 Although, we did not detect any mutations at/or near the YXXM coding regions in patients" DNA, immunprecipitation analysis of IRS1 indicated decreased levels of expression and tyrosine phosphorylation of IRS1 in patient"s samples compared to that of healthy controls. Tyrosine 176-184 insulin receptor substrate 1 Homo sapiens 126-130 26950447-7 2016 Although, we did not detect any mutations at/or near the YXXM coding regions in patients" DNA, immunprecipitation analysis of IRS1 indicated decreased levels of expression and tyrosine phosphorylation of IRS1 in patient"s samples compared to that of healthy controls. Tyrosine 176-184 insulin receptor substrate 1 Homo sapiens 204-208 26143144-4 2015 Insulin-stimulated glucose uptake, phosphorylation of PKB, IRS-1-associated PI3K, and IRS-1 tyrosine phosphorylation were all inhibited by ET-1 and 8-bromo cAMP in a synergistic manner. Tyrosine 92-100 insulin receptor substrate 1 Homo sapiens 86-91 26143144-6 2015 In addition, after correction for the loss in IRS-1 protein, the inhibition of insulin-stimulated IRS-1 tyrosine phosphorylation or IRS-1-associated PI3K was mainly caused by cAMP. Tyrosine 104-112 insulin receptor substrate 1 Homo sapiens 46-51 26143144-6 2015 In addition, after correction for the loss in IRS-1 protein, the inhibition of insulin-stimulated IRS-1 tyrosine phosphorylation or IRS-1-associated PI3K was mainly caused by cAMP. Tyrosine 104-112 insulin receptor substrate 1 Homo sapiens 98-103 26143144-6 2015 In addition, after correction for the loss in IRS-1 protein, the inhibition of insulin-stimulated IRS-1 tyrosine phosphorylation or IRS-1-associated PI3K was mainly caused by cAMP. Tyrosine 104-112 insulin receptor substrate 1 Homo sapiens 98-103 25813876-5 2015 In this study, we found an increase in IRS-1 phosphorylation at Ser636 and decrease in tyrosine phosphorylation, which accelerated IRS-1 turnover and reduced insulin-Akt signaling in alpha-Syn-overexpressing SK-N-SH cells and transgenic mice. Tyrosine 87-95 insulin receptor substrate 1 Homo sapiens 131-136 25815690-7 2015 PA attenuated insulin-mediated insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation, leading to decreased glucose uptake, and phosphorylation of eNOS, leading to a reduction in the production of NO. Tyrosine 68-76 insulin receptor substrate 1 Homo sapiens 61-66 26404168-7 2015 This was associated with reduced serine phosphorylation of insulin receptor substrate-1 (IRS-1) and improved insulin-stimulated tyrosine phosphorylation of IRS-1 and downstream activation of Akt phosphorylation. Tyrosine 128-136 insulin receptor substrate 1 Homo sapiens 156-161 26108617-6 2015 Inhibition of glucosylceramide and ganglioside synthesis results in improved insulin sensitivity and increased activatory tyrosine phosphorylation of IRS1 in the muscle. Tyrosine 122-130 insulin receptor substrate 1 Homo sapiens 150-154 25944785-5 2015 METHODS AND RESULTS: In human visceral adipocytes, PCA stimulated insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation (+40% with respect to untreated cells) and the downstream events, i.e. phosphoinositide 3-kinase binding to IRS-1 and Akt phosphorylation (+100%, +180%, respectively, with respect to untreated cells). Tyrosine 103-111 insulin receptor substrate 1 Homo sapiens 66-94 25944785-5 2015 METHODS AND RESULTS: In human visceral adipocytes, PCA stimulated insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation (+40% with respect to untreated cells) and the downstream events, i.e. phosphoinositide 3-kinase binding to IRS-1 and Akt phosphorylation (+100%, +180%, respectively, with respect to untreated cells). Tyrosine 103-111 insulin receptor substrate 1 Homo sapiens 96-101 25875045-8 2015 Consistent with this notion, Ucn 2 reduced insulin-induced tyrosine phosphorylation of IRS-1, and treatment with rapamycin reversed the inhibitory effect of Ucn 2 on IRS-1 and Akt phosphorylation. Tyrosine 59-67 insulin receptor substrate 1 Homo sapiens 87-92 25667086-6 2015 Insulin receptor substrate-1 (IRS-1) is recruited to interact with the IR-catalyzed phospho-tyrosine cav-2, which facilitates IRS-1 association with and activation by IR to initiate IRS-1-mediated downstream signaling. Tyrosine 92-100 insulin receptor substrate 1 Homo sapiens 30-35 25667086-6 2015 Insulin receptor substrate-1 (IRS-1) is recruited to interact with the IR-catalyzed phospho-tyrosine cav-2, which facilitates IRS-1 association with and activation by IR to initiate IRS-1-mediated downstream signaling. Tyrosine 92-100 insulin receptor substrate 1 Homo sapiens 126-131 25667086-6 2015 Insulin receptor substrate-1 (IRS-1) is recruited to interact with the IR-catalyzed phospho-tyrosine cav-2, which facilitates IRS-1 association with and activation by IR to initiate IRS-1-mediated downstream signaling. Tyrosine 92-100 insulin receptor substrate 1 Homo sapiens 126-131 25667086-7 2015 Cav-2 fatty acylation and tyrosine phosphorylation are necessary for the IRS-1-dependent PI3K-Akt and ERK activations responsible for glucose uptake and cell survival and proliferation. Tyrosine 26-34 insulin receptor substrate 1 Homo sapiens 73-78 25784556-11 2015 They provide internal feedback, mediated by Ser(P)(473)-AKT, Ser(P)(401)-GATA2, and nuclear GATA2, which links the opposing effects of serine and tyrosine phosphorylations of IRS1 and can modulate insulin responsiveness. Tyrosine 146-154 insulin receptor substrate 1 Homo sapiens 175-179 25784556-5 2015 GRB10 silencing blocked the carrageenan-induced reduction of the insulin-stimulated increase in Tyr(P)-IRS1 and partially reversed the decline in Ser(P)(473)-AKT. Tyrosine 96-99 insulin receptor substrate 1 Homo sapiens 103-107 24652289-6 2014 Insulin-stimulated Irs1 tyrosine phosphorylation (Tyr(P)(Irs1)) was enhanced by inhibition of the PI3K Akt mTOR pathway and correlated with decreased Ser(P)-302(Irs1), Ser(P)-307(Irs1), Ser(P)-318(Irs1), Ser(P)-325(Irs1), and Ser(P)-346(Irs1). Tyrosine 24-32 insulin receptor substrate 1 Homo sapiens 19-23 25586176-3 2015 GKAP42 knockdown in 3T3-L1 adipocytes suppressed insulin-dependent IRS-1 tyrosine phosphorylation and downstream signaling, resulting in suppression of GLUT4 translocation to plasma membrane induced by insulin. Tyrosine 73-81 insulin receptor substrate 1 Homo sapiens 67-72 25586176-8 2015 These data indicated that TNF-alpha-induced repression of GKAP42 via cGK-Ialpha caused reduction of insulin-induced IRS-1 tyrosine phosphorylation at least in part. Tyrosine 122-130 insulin receptor substrate 1 Homo sapiens 116-121 25120613-8 2014 After insulin stimulation, IRS1 was tyrosine-phosphorylated to a greater extent in control adipocytes compared with darunavir-treated adipocytes. Tyrosine 36-44 insulin receptor substrate 1 Homo sapiens 27-31 25120613-9 2014 Tyrosine phosphorylation of IRS1 was inhibited in lopinavir-treated adipocytes. Tyrosine 0-8 insulin receptor substrate 1 Homo sapiens 28-32 25606440-2 2014 The tyrosine phosphorylation of IRS1 serves as docking molecules for downstream effectors such as Phosphatidylinositol 3-kinase and phosphotyrosine phosphatase-2. Tyrosine 4-12 insulin receptor substrate 1 Homo sapiens 32-36 25606440-3 2014 We focused on the Gly972Arg and Ala513Pro variants of the IRS1 gene, since these specific allelic variants are located near the Tyr-Met-X-Met (YMXM) motifs around Tyr987 and Tyr612. Tyrosine 128-131 insulin receptor substrate 1 Homo sapiens 58-62 25445050-8 2015 F015 also inhibited inflammation-stimulated IRS-1 serine phosphorylation and restored insulin-stimulated IRS-1 tyrosine phosphorylation in presence of palmitate, resulted in enhanced insulin sensitivity. Tyrosine 111-119 insulin receptor substrate 1 Homo sapiens 105-110 25556062-6 2014 mSMS enhanced AMPK phosphorylation and promoted basal glucose uptake in adipocytes; mSMS inhibited NF-kappaB activation by reducing P65 phosphorylation and improved insulin-stimulated IRS-1 tyrosine and Akt phosphorylation, leading to the restoration of insulin-mediated glucose uptake when cells were exposed to inflammatory stimulation. Tyrosine 190-198 insulin receptor substrate 1 Homo sapiens 184-189 24652289-6 2014 Insulin-stimulated Irs1 tyrosine phosphorylation (Tyr(P)(Irs1)) was enhanced by inhibition of the PI3K Akt mTOR pathway and correlated with decreased Ser(P)-302(Irs1), Ser(P)-307(Irs1), Ser(P)-318(Irs1), Ser(P)-325(Irs1), and Ser(P)-346(Irs1). Tyrosine 24-32 insulin receptor substrate 1 Homo sapiens 57-61 24652289-6 2014 Insulin-stimulated Irs1 tyrosine phosphorylation (Tyr(P)(Irs1)) was enhanced by inhibition of the PI3K Akt mTOR pathway and correlated with decreased Ser(P)-302(Irs1), Ser(P)-307(Irs1), Ser(P)-318(Irs1), Ser(P)-325(Irs1), and Ser(P)-346(Irs1). Tyrosine 24-32 insulin receptor substrate 1 Homo sapiens 57-61 24652289-6 2014 Insulin-stimulated Irs1 tyrosine phosphorylation (Tyr(P)(Irs1)) was enhanced by inhibition of the PI3K Akt mTOR pathway and correlated with decreased Ser(P)-302(Irs1), Ser(P)-307(Irs1), Ser(P)-318(Irs1), Ser(P)-325(Irs1), and Ser(P)-346(Irs1). Tyrosine 24-32 insulin receptor substrate 1 Homo sapiens 57-61 24652289-6 2014 Insulin-stimulated Irs1 tyrosine phosphorylation (Tyr(P)(Irs1)) was enhanced by inhibition of the PI3K Akt mTOR pathway and correlated with decreased Ser(P)-302(Irs1), Ser(P)-307(Irs1), Ser(P)-318(Irs1), Ser(P)-325(Irs1), and Ser(P)-346(Irs1). Tyrosine 24-32 insulin receptor substrate 1 Homo sapiens 57-61 24652289-6 2014 Insulin-stimulated Irs1 tyrosine phosphorylation (Tyr(P)(Irs1)) was enhanced by inhibition of the PI3K Akt mTOR pathway and correlated with decreased Ser(P)-302(Irs1), Ser(P)-307(Irs1), Ser(P)-318(Irs1), Ser(P)-325(Irs1), and Ser(P)-346(Irs1). Tyrosine 24-32 insulin receptor substrate 1 Homo sapiens 57-61 24652289-6 2014 Insulin-stimulated Irs1 tyrosine phosphorylation (Tyr(P)(Irs1)) was enhanced by inhibition of the PI3K Akt mTOR pathway and correlated with decreased Ser(P)-302(Irs1), Ser(P)-307(Irs1), Ser(P)-318(Irs1), Ser(P)-325(Irs1), and Ser(P)-346(Irs1). Tyrosine 24-32 insulin receptor substrate 1 Homo sapiens 57-61 24652289-6 2014 Insulin-stimulated Irs1 tyrosine phosphorylation (Tyr(P)(Irs1)) was enhanced by inhibition of the PI3K Akt mTOR pathway and correlated with decreased Ser(P)-302(Irs1), Ser(P)-307(Irs1), Ser(P)-318(Irs1), Ser(P)-325(Irs1), and Ser(P)-346(Irs1). Tyrosine 50-53 insulin receptor substrate 1 Homo sapiens 19-23 24652289-6 2014 Insulin-stimulated Irs1 tyrosine phosphorylation (Tyr(P)(Irs1)) was enhanced by inhibition of the PI3K Akt mTOR pathway and correlated with decreased Ser(P)-302(Irs1), Ser(P)-307(Irs1), Ser(P)-318(Irs1), Ser(P)-325(Irs1), and Ser(P)-346(Irs1). Tyrosine 50-53 insulin receptor substrate 1 Homo sapiens 57-61 24652289-6 2014 Insulin-stimulated Irs1 tyrosine phosphorylation (Tyr(P)(Irs1)) was enhanced by inhibition of the PI3K Akt mTOR pathway and correlated with decreased Ser(P)-302(Irs1), Ser(P)-307(Irs1), Ser(P)-318(Irs1), Ser(P)-325(Irs1), and Ser(P)-346(Irs1). Tyrosine 50-53 insulin receptor substrate 1 Homo sapiens 57-61 24652289-6 2014 Insulin-stimulated Irs1 tyrosine phosphorylation (Tyr(P)(Irs1)) was enhanced by inhibition of the PI3K Akt mTOR pathway and correlated with decreased Ser(P)-302(Irs1), Ser(P)-307(Irs1), Ser(P)-318(Irs1), Ser(P)-325(Irs1), and Ser(P)-346(Irs1). Tyrosine 50-53 insulin receptor substrate 1 Homo sapiens 57-61 24652289-6 2014 Insulin-stimulated Irs1 tyrosine phosphorylation (Tyr(P)(Irs1)) was enhanced by inhibition of the PI3K Akt mTOR pathway and correlated with decreased Ser(P)-302(Irs1), Ser(P)-307(Irs1), Ser(P)-318(Irs1), Ser(P)-325(Irs1), and Ser(P)-346(Irs1). Tyrosine 50-53 insulin receptor substrate 1 Homo sapiens 57-61 24652289-6 2014 Insulin-stimulated Irs1 tyrosine phosphorylation (Tyr(P)(Irs1)) was enhanced by inhibition of the PI3K Akt mTOR pathway and correlated with decreased Ser(P)-302(Irs1), Ser(P)-307(Irs1), Ser(P)-318(Irs1), Ser(P)-325(Irs1), and Ser(P)-346(Irs1). Tyrosine 50-53 insulin receptor substrate 1 Homo sapiens 57-61 24652289-6 2014 Insulin-stimulated Irs1 tyrosine phosphorylation (Tyr(P)(Irs1)) was enhanced by inhibition of the PI3K Akt mTOR pathway and correlated with decreased Ser(P)-302(Irs1), Ser(P)-307(Irs1), Ser(P)-318(Irs1), Ser(P)-325(Irs1), and Ser(P)-346(Irs1). Tyrosine 50-53 insulin receptor substrate 1 Homo sapiens 57-61 24652289-8 2014 Thus, IRS1 Ser(P)/Thr(P) is an integrated response to insulin stimulation and metabolic stress, which associates with reduced Tyr(P)(Irs1) in CHO(IR)/IRS1 cells. Tyrosine 126-129 insulin receptor substrate 1 Homo sapiens 6-10 24652289-8 2014 Thus, IRS1 Ser(P)/Thr(P) is an integrated response to insulin stimulation and metabolic stress, which associates with reduced Tyr(P)(Irs1) in CHO(IR)/IRS1 cells. Tyrosine 126-129 insulin receptor substrate 1 Homo sapiens 133-137 24652289-8 2014 Thus, IRS1 Ser(P)/Thr(P) is an integrated response to insulin stimulation and metabolic stress, which associates with reduced Tyr(P)(Irs1) in CHO(IR)/IRS1 cells. Tyrosine 126-129 insulin receptor substrate 1 Homo sapiens 150-154 24068609-7 2014 In CIE-treated cells, there was reduced IR expression, incomplete IRS-1 adaptation, lack of signalling pathway attenuation and contra-adaptive increases in IRS-1 tyrosine phosphorylation in several cell types. Tyrosine 162-170 insulin receptor substrate 1 Homo sapiens 156-161 24337154-6 2014 RESULTS: Lipid infusion impaired insulin-stimulated IRS-1 tyrosine phosphorylation and reduced peripheral insulin sensitivity (p < 0.01). Tyrosine 58-66 insulin receptor substrate 1 Homo sapiens 52-57 24337154-10 2014 In summary, insulin resistance induced by prolonged low-dose lipid infusion occurs together with increased TLR-driven inflammatory signalling and impaired insulin-stimulated IRS-1 tyrosine phosphorylation. Tyrosine 180-188 insulin receptor substrate 1 Homo sapiens 174-179 24341419-4 2014 The insulin resistance in normal glucose tolerance pregnancy is related to a decrease in the post-receptor insulin signalling cascade, specifically decreased insulin receptor substrate 1 tyrosine phosphorylation. Tyrosine 187-195 insulin receptor substrate 1 Homo sapiens 158-186 24341419-6 2014 In contrast, in gestational diabetes, in addition to the decrease in insulin receptor substrate 1 tyrosine phosphorylation, there is an additional decrease in tyrosine phosphorylation of the intracellular portion of the insulin receptor that is not related to the insulin receptor protein content. Tyrosine 98-106 insulin receptor substrate 1 Homo sapiens 69-97 25580119-3 2014 Two important insulin receptor substrates 1 and 2 are widely expressed in human, and alternative phosphorylation on their serine (Ser) and threonine (Thr) residues has been known to block the Tyr phosphorylation of IRSs, thus inhibiting insulin signaling and promoting insulin resistance. Tyrosine 192-195 insulin receptor substrate 1 Homo sapiens 14-49 23460259-7 2013 In addition, HepG2 cells with reduced level of GRK2 also demonstrated increased tyrosine phosphorylation of IRS1 at the residue 612 and increased phosphorylation of Akt, indicating a stronger activation of IGF-1R signaling pathway. Tyrosine 80-88 insulin receptor substrate 1 Homo sapiens 108-112 23831466-3 2013 An insulin resistance state was induced by exposing cells to 30mM glucose, as indicated by reduced insulin-stimulated tyrosine phosphorylation of IRS-1 and glucose uptake. Tyrosine 118-126 insulin receptor substrate 1 Homo sapiens 146-151 23831466-7 2013 Taken together, our findings suggest a link between high glucose and insulin resistance in muscle cells, and provide further evidence that pinusolide attenuates blockade of insulin signaling by enhancing IRS-1 tyrosine phosphorylation by the activating the AMPK pathway. Tyrosine 210-218 insulin receptor substrate 1 Homo sapiens 204-209 23481042-4 2013 PDGF inhibited IGF-I-stimulated IRS-1 tyrosine phosphorylation and subsequent IGF-I-induced PI 3-kinase activity, and stimulated IRS-1 serine 307 phosphorylation. Tyrosine 38-46 insulin receptor substrate 1 Homo sapiens 32-37 23274913-7 2013 Overexpression of NYGGF4 significantly inhibited tyrosine phosphorylation of Insulin receptor substrate 1 (IRS-1) and serine phosphorylation of Akt, whereas overexpression of TFAM strongly induced phosphorylation of IRS-1 and Akt in NYGGF4-overexpressing adipocytes. Tyrosine 49-57 insulin receptor substrate 1 Homo sapiens 77-105 23274913-7 2013 Overexpression of NYGGF4 significantly inhibited tyrosine phosphorylation of Insulin receptor substrate 1 (IRS-1) and serine phosphorylation of Akt, whereas overexpression of TFAM strongly induced phosphorylation of IRS-1 and Akt in NYGGF4-overexpressing adipocytes. Tyrosine 49-57 insulin receptor substrate 1 Homo sapiens 107-112 23404947-5 2013 Chronic leucine supplementation did not enhance insulin receptor substract-1 (IRS-1) phosphorylation on serine 302, but elevated basal IRS-1 phosphorylation on tyrosine 632 and improved insulin-stimulated protein kinase B (Akt) and mammalian target of rapamycin (mTOR) phosphorylation in liver, skeletal muscle, and adipose tissue of rats on HFD rats, indicating leucine supplementation prevented HFD-induced insulin resistance in insulin-target tissues. Tyrosine 160-168 insulin receptor substrate 1 Homo sapiens 135-140 23463119-8 2013 Insulin signaling defects in hepatic IRS-1 tyrosine phosphorylation and PI3-kinase association/activation may contribute to IR, which leads to the development of T2D in patients with HCV infection. Tyrosine 43-51 insulin receptor substrate 1 Homo sapiens 37-42 23504962-9 2013 Quercetin and quercetin-3-O-glucuronide facilitated PI3K signaling by positive regulation of serine/tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and restoration of downstream Akt/eNOS activation, leading to an increased insulin-mediated NO level. Tyrosine 100-108 insulin receptor substrate 1 Homo sapiens 128-156 23478262-6 2013 Furthermore, deletion of AP-1 binding sites in IRS-1 impaired IGF-I-induced cell proliferation, accompanied by reduced tyrosine phosphorylation of IRS-1 and its association with phosphoinositide (PI) 3-kinase. Tyrosine 119-127 insulin receptor substrate 1 Homo sapiens 47-52 23478262-6 2013 Furthermore, deletion of AP-1 binding sites in IRS-1 impaired IGF-I-induced cell proliferation, accompanied by reduced tyrosine phosphorylation of IRS-1 and its association with phosphoinositide (PI) 3-kinase. Tyrosine 119-127 insulin receptor substrate 1 Homo sapiens 147-152 23566306-5 2013 GF induced phosphorylation of MKK7 and JNK, phosphorylation of serine307 on IRS-1, and reduced tyrosine phosphorylation of IRS-1 and -2. Tyrosine 95-103 insulin receptor substrate 1 Homo sapiens 123-135 23174405-9 2013 Conversely, insulin stimulation of tyrosine phosphorylated IRS-1 was absent and serine 307 phosphorylation of IRS-1 was increased on HF/LC, with blunting of IRS-1-associated PI3-kinase activity. Tyrosine 35-43 insulin receptor substrate 1 Homo sapiens 59-64 22968630-4 2012 NYGGF4 overexpression resulted in significant inhibition of tyrosine phosphorylation of IRS-1 and serine phosphorylation of Akt, whereas incubation with metformin strongly activated IRS-1 and Akt phosphorylation in NYGGF4 overexpression adipocytes. Tyrosine 60-68 insulin receptor substrate 1 Homo sapiens 88-93 23190749-10 2013 Kakkalide facilitated PI3K signaling by positively regulating serine/tyrosine phosphorylation of IRS-1. Tyrosine 69-77 insulin receptor substrate 1 Homo sapiens 97-102 23983791-8 2013 In mature 3T3-L1 adipocytes, naringenin reduced the ability of insulin to induce IRS-1 tyrosine phosphorylation and substantially inhibited insulin-stimulated glucose uptake in a dose-dependent manner and over a time frame of 1.5 to 24 hours. Tyrosine 87-95 insulin receptor substrate 1 Homo sapiens 81-86 23565163-1 2013 The insulin receptor substrate-1 (IRS1) is phosphorylated on serine 307 (human sequence, corresponding to murine serine 302) in response to insulin as part of a feedback loop that controls IRS1 phosphorylation on tyrosine residues by the insulin receptor. Tyrosine 213-221 insulin receptor substrate 1 Homo sapiens 4-32 23565163-1 2013 The insulin receptor substrate-1 (IRS1) is phosphorylated on serine 307 (human sequence, corresponding to murine serine 302) in response to insulin as part of a feedback loop that controls IRS1 phosphorylation on tyrosine residues by the insulin receptor. Tyrosine 213-221 insulin receptor substrate 1 Homo sapiens 34-38 23174405-8 2013 Skeletal muscle of the LF/HC group had increased insulin-stimulated tyrosine phosphorylation of IRS-1, decreased insulin-stimulated Ser307 phosphorylation of IRS-1, and increased IRS-1-associated phosphatidylinositol (PI)3-kinase activity. Tyrosine 68-76 insulin receptor substrate 1 Homo sapiens 96-101 23073384-6 2012 Elevated IRS1 (pan-tyr) and GSK3beta (ser-9) phosphorylation were observed in two novel IGF1R variants with receptor L domain mutations. Tyrosine 19-22 insulin receptor substrate 1 Homo sapiens 9-13 22728334-2 2012 Insulin receptor substrate-1 (IRS1) plays a key role in insulin signaling, the function of which is regulated by both phosphorylation and dephosphorylation of tyrosine and serine/threonine residues. Tyrosine 159-167 insulin receptor substrate 1 Homo sapiens 0-28 23182460-10 2012 NOD1 activation weakened insulin signal transduction as revealed by increased JNK and IRS-1 Ser307 phosphorylation, inhibited IRS-1 tyrosine phosphorylation, and reduced insulin-induced phosphorylation of Akt on Ser473 and Thr308 in human adipocytes. Tyrosine 132-140 insulin receptor substrate 1 Homo sapiens 126-131 22820890-5 2012 These changes were accompanied by a marked upregulation in expression of insulin-stimulated tyrosine phosphorylation of IRS-1 and serine phosphorylation of Akt following treatment with alpha-LA. Tyrosine 92-100 insulin receptor substrate 1 Homo sapiens 120-125 23045700-6 2012 PKA uses a route that promotes phosphorylation of insulin receptor substrate-1 (IRS-1) on Tyr(989), a canonical binding site for the 85-kDa regulatory subunit of PI3K that allosterically activates the catalytic subunit. Tyrosine 90-93 insulin receptor substrate 1 Homo sapiens 50-78 23045700-6 2012 PKA uses a route that promotes phosphorylation of insulin receptor substrate-1 (IRS-1) on Tyr(989), a canonical binding site for the 85-kDa regulatory subunit of PI3K that allosterically activates the catalytic subunit. Tyrosine 90-93 insulin receptor substrate 1 Homo sapiens 80-85 22728334-2 2012 Insulin receptor substrate-1 (IRS1) plays a key role in insulin signaling, the function of which is regulated by both phosphorylation and dephosphorylation of tyrosine and serine/threonine residues. Tyrosine 159-167 insulin receptor substrate 1 Homo sapiens 30-34 22766331-8 2012 Meanwhile, diosgenin attenuated PA-induced serine phosphorylation (S307) of IRS-1 and restored IRS-1 tyrosine phosphorylation in response to insulin. Tyrosine 101-109 insulin receptor substrate 1 Homo sapiens 95-100 22609131-7 2012 TNF-alpha, secreted by hypertrophic adipocytes and adipose tissue macrophages, also inhibits IR signaling by a double mechanism of serine-phosphorylation and tyrosine-dephosphorylation of IRS-1, causing inactivation and degradation of IRS-1 and a consequent stop of IR signaling. Tyrosine 158-166 insulin receptor substrate 1 Homo sapiens 188-193 22766331-9 2012 The beneficial modulation of serine/tyrosine phosphorylation of IRS-1 by diosgenin contributed to the improvement of insulin signaling along PI3K/Akt/eNOS pathways and thereby increased insulin-mediated NO production. Tyrosine 36-44 insulin receptor substrate 1 Homo sapiens 64-69 21804605-2 2012 We previously showed that insulin-like growth factor 1 receptor (IGF1R) is essential for EN-mediated oncogenesis and that insulin receptor substrate 1 (IRS1) is constitutively tyrosine phosphorylated and bound by EN in transformed cells. Tyrosine 176-184 insulin receptor substrate 1 Homo sapiens 122-150 22355071-9 2012 Moreover, insulin"s ability to increase IRS-1 tyrosine 612 and serine 632/635 phosphorylation was attenuated by ROCK1 suppression. Tyrosine 46-54 insulin receptor substrate 1 Homo sapiens 40-45 22528396-5 2012 NYGGF4 overexpression resulted in significant inhibition of tyrosine phosphorylation of IRS-1 and serine phosphorylation of Akt, whereas incubation with LA strongly activated IRS-1 and Akt phosphorylation in NYGGF4 overexpression adipocytes. Tyrosine 60-68 insulin receptor substrate 1 Homo sapiens 88-93 21804605-2 2012 We previously showed that insulin-like growth factor 1 receptor (IGF1R) is essential for EN-mediated oncogenesis and that insulin receptor substrate 1 (IRS1) is constitutively tyrosine phosphorylated and bound by EN in transformed cells. Tyrosine 176-184 insulin receptor substrate 1 Homo sapiens 152-156 21804605-5 2012 We find that both IRS1 and kinase active IGF1R are required for EN transformation, that tyrosine phosphorylated IRS1 is present in high molecular weight complexes with EN and IGF1R, and that EN colocalizes with IGF1R at the plasma membrane. Tyrosine 88-96 insulin receptor substrate 1 Homo sapiens 112-116 22207502-11 2012 Glucose deprivation enhanced tyrosine phosphorylation of IRS-1 and the insulin receptor, effects that were blocked by AMPK inhibition and mimicked by AICAR. Tyrosine 29-37 insulin receptor substrate 1 Homo sapiens 57-62 22281494-2 2012 Pretreatment with 5mug/ml of tunicamycin or 600nM thapsigargin for 3h decreased insulin-mediated tyrosine phosphorylation of IRS-1 and glucose uptake, and increased the level of mTOR/S6K1 phosphorylation in L6 myotubes. Tyrosine 97-105 insulin receptor substrate 1 Homo sapiens 125-130 22158866-3 2012 In this study, it was observed that PKC activation differentially inhibited insulin receptor substrate 1/2 (IRS1/2) signaling of insulin"s activation of PI3K/eNOS by decreasing only tyrosine phosphorylation of IRS2. Tyrosine 182-190 insulin receptor substrate 1 Homo sapiens 76-106 22158866-3 2012 In this study, it was observed that PKC activation differentially inhibited insulin receptor substrate 1/2 (IRS1/2) signaling of insulin"s activation of PI3K/eNOS by decreasing only tyrosine phosphorylation of IRS2. Tyrosine 182-190 insulin receptor substrate 1 Homo sapiens 108-114 22281494-3 2012 However, the inhibition of mTOR activity by rapamycin (inhibitor of several intracellular pathways including S6K1 pathways) reversed the ER stress-reduced tyrosine phosphorylation of IRS-1 and glucose uptake. Tyrosine 155-163 insulin receptor substrate 1 Homo sapiens 183-188 22227580-1 2012 Insulin receptor substrate-1 (IRS-1) is a key protein in the insulin-like growth factor (IGF) signaling whose tyrosine phosphorylation by the type 1 IGF receptor is necessary for the recruitment and activation of the downstream effectors. Tyrosine 110-118 insulin receptor substrate 1 Homo sapiens 0-28 22227580-1 2012 Insulin receptor substrate-1 (IRS-1) is a key protein in the insulin-like growth factor (IGF) signaling whose tyrosine phosphorylation by the type 1 IGF receptor is necessary for the recruitment and activation of the downstream effectors. Tyrosine 110-118 insulin receptor substrate 1 Homo sapiens 30-35 22227580-3 2012 EGF and FGF inhibited IGF-I-stimulated tyrosine phosphorylation of IRS-1 and the subsequent IGF-I-induced phosphatidylinositol 3-kinase (PI 3-kinase) activity. Tyrosine 39-47 insulin receptor substrate 1 Homo sapiens 67-72 22227580-7 2012 Interestingly, specific inhibition of either PI 3-kinase or PKD1 totally impaired EGF- or FGF-induced inhibition of IGF-I-stimulated IRS-1 tyrosine phosphorylation. Tyrosine 139-147 insulin receptor substrate 1 Homo sapiens 133-138 22006247-10 2012 Indeed, tunicamycin induced a robust activation of the inositol-requiring enzyme 1 (IRE-1)/c-JUN NH2-terminal kinase (JNK) pathway, leading to serine phosphorylation of insulin receptor substrate 1 (IRS-1) and a decrease in IRS-1 tyrosine phosphorylation. Tyrosine 230-238 insulin receptor substrate 1 Homo sapiens 169-197 22006247-10 2012 Indeed, tunicamycin induced a robust activation of the inositol-requiring enzyme 1 (IRE-1)/c-JUN NH2-terminal kinase (JNK) pathway, leading to serine phosphorylation of insulin receptor substrate 1 (IRS-1) and a decrease in IRS-1 tyrosine phosphorylation. Tyrosine 230-238 insulin receptor substrate 1 Homo sapiens 199-204 22028447-5 2012 Mammalian target of rapamycin activation caused serine phosphorylation of insulin receptor substrate-1, which attenuated insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1 and glucose uptake. Tyrosine 140-148 insulin receptor substrate 1 Homo sapiens 74-102 22028447-5 2012 Mammalian target of rapamycin activation caused serine phosphorylation of insulin receptor substrate-1, which attenuated insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1 and glucose uptake. Tyrosine 140-148 insulin receptor substrate 1 Homo sapiens 168-196 21289241-5 2011 RESULTS: GDM women had decreased skeletal muscle insulin-stimulated insulin receptor and insulin receptor substrate 1 (IRS1) tyrosine activation and reduced IRS1, concomitant with increased basal IRS1 serine phosphorylation and basal p70 S6-kinase (S6K1) activation, which resolved postpartum. Tyrosine 125-133 insulin receptor substrate 1 Homo sapiens 119-123 21937042-5 2011 RESULTS: ATII induces IRS-1 phosphorylation at Ser(312) and Ser(616) through the activation of JNK and ERK 1/2, resulting in the inhibition of the insulin-induced phosphorylation of IRS1 tyrosines, Akt and eNOS. Tyrosine 187-196 insulin receptor substrate 1 Homo sapiens 22-27 21786209-7 2011 In addition, betel nut extract and arecoline increased the basal level of IRS-1 serine(307) phosphorylation and decreased insulin-stimulated IRS-1 tyrosine, Akt, and PI3 kinase phosphorylation. Tyrosine 147-155 insulin receptor substrate 1 Homo sapiens 141-146 21664164-6 2011 RESULTS: Compared with cells from non-diabetic subjects, adipocytes from T2DM patients showed signs of insulin resistance, with significantly reduced IRS-1 tyrosine and AKT (Ser 473) phosphorylation levels in response to insulin stimulation. Tyrosine 156-164 insulin receptor substrate 1 Homo sapiens 150-155 21664164-8 2011 Introduction of NF-kappaB decoy molecules significantly inhibited both IL-6 secretion and NF-kappaB activity, while enhancing insulin-stimulated IRS-1 tyrosine and AKT (Ser473) phosphorylation in T2DM adipocytes. Tyrosine 151-159 insulin receptor substrate 1 Homo sapiens 145-150 22629383-9 2012 A significant decrease in IRS-1 tyrosine-phosphorylation in the WCP was also associated with the presence (p<0.02) and severity (p<0.02) of HAND. Tyrosine 32-40 insulin receptor substrate 1 Homo sapiens 26-31 21386060-3 2011 IFN-beta suppressed insulin-induced tyrosine phosphorylation of IRS-1 without affecting its expression, whereas IFN-gamma reduced both the protein level and tyrosine phosphorylation. Tyrosine 36-44 insulin receptor substrate 1 Homo sapiens 64-69 20185348-11 2010 Serine phosphorylation of IRS-1 was strongly induced and the insulin-dependent tyrosine phosphorylation of IRS-1 was suppressed by preincubating the adipocytes with IGF-I. Tyrosine 79-87 insulin receptor substrate 1 Homo sapiens 107-112 20685959-4 2010 We found that PKR up-regulates the inhibitory phosphorylation of IRS1 at Ser312, which suppresses the tyrosine phosphorylation of IRS1. Tyrosine 102-110 insulin receptor substrate 1 Homo sapiens 65-69 20685959-4 2010 We found that PKR up-regulates the inhibitory phosphorylation of IRS1 at Ser312, which suppresses the tyrosine phosphorylation of IRS1. Tyrosine 102-110 insulin receptor substrate 1 Homo sapiens 130-134 21386060-6 2011 In addition, adenovirus-mediated overexpression of either SOCS1 or SOCS3 inhibited insulin-induced tyrosine phosphorylation of IRS-1, whereas the reduction of IRS-1 protein was observed only in SOCS3-expressed cells. Tyrosine 99-107 insulin receptor substrate 1 Homo sapiens 127-132 21386060-7 2011 Notably, IFN-beta-induced SOCS1 expression and suppression of insulin-induced tyrosine phosphorylation of IRS-1 were attenuated by siRNA-mediated knockdown of STAT1. Tyrosine 78-86 insulin receptor substrate 1 Homo sapiens 106-111 21321112-8 2011 The loss of Egr-1 function, knockdown of GGPPS, or inhibition of Erk1/2 activity in insulin-resistant adipocytes restored insulin receptor substrate-1 tyrosine phosphorylation and increased insulin sensitivity. Tyrosine 151-159 insulin receptor substrate 1 Homo sapiens 122-150 21189360-4 2011 Insulin-stimulated IRS-1 tyrosine phosphorylation is impaired 41-48% in diabetic subjects compared with lean or obese subjects. Tyrosine 25-33 insulin receptor substrate 1 Homo sapiens 19-24 20594757-10 2011 The level of IRS-1 serine307 phosphorylation in muscle in vivo significantly increased after burn (P < 0.01), while insulin-induced tyrosine phosphorylation of IRS-1 significantly decreased (P < 0.01). Tyrosine 135-143 insulin receptor substrate 1 Homo sapiens 163-168 21168390-7 2011 Results of the in vitro tyrosine phosphorylation assay indicated that tyrosine phosphorylation of IRS-1 by insulin receptor was decreased when IRS-1 was contained in IRSomes prepared from 3T3-L1 adipocytes treated with TNF-alpha. Tyrosine 24-32 insulin receptor substrate 1 Homo sapiens 98-103 21168390-7 2011 Results of the in vitro tyrosine phosphorylation assay indicated that tyrosine phosphorylation of IRS-1 by insulin receptor was decreased when IRS-1 was contained in IRSomes prepared from 3T3-L1 adipocytes treated with TNF-alpha. Tyrosine 24-32 insulin receptor substrate 1 Homo sapiens 143-148 21168390-7 2011 Results of the in vitro tyrosine phosphorylation assay indicated that tyrosine phosphorylation of IRS-1 by insulin receptor was decreased when IRS-1 was contained in IRSomes prepared from 3T3-L1 adipocytes treated with TNF-alpha. Tyrosine 70-78 insulin receptor substrate 1 Homo sapiens 98-103 21168390-7 2011 Results of the in vitro tyrosine phosphorylation assay indicated that tyrosine phosphorylation of IRS-1 by insulin receptor was decreased when IRS-1 was contained in IRSomes prepared from 3T3-L1 adipocytes treated with TNF-alpha. Tyrosine 70-78 insulin receptor substrate 1 Homo sapiens 143-148 20594869-2 2010 Insulin signaling is dependent on specific protein phosphorylation events, and analysis of insulin receptor substrate-1 (IRS-1) phosphorylation reveals a complex interplay between tyrosine, serine, and threonine phosphorylation. Tyrosine 180-188 insulin receptor substrate 1 Homo sapiens 91-119 20594869-2 2010 Insulin signaling is dependent on specific protein phosphorylation events, and analysis of insulin receptor substrate-1 (IRS-1) phosphorylation reveals a complex interplay between tyrosine, serine, and threonine phosphorylation. Tyrosine 180-188 insulin receptor substrate 1 Homo sapiens 121-126 20601126-4 2010 We found that Ang II significantly inhibited insulin-induced phosphorylation of tyrosine 608 of IRS-1 and serine 473 of Akt, a downstream member of anti-mitogenic pathway of insulin. Tyrosine 80-88 insulin receptor substrate 1 Homo sapiens 96-101 20185348-12 2010 Further, NAC restored these changes induced by IGF-I on both serine and tyrosine phosphorylation of IRS-1. Tyrosine 72-80 insulin receptor substrate 1 Homo sapiens 100-105 20060191-4 2010 In cultured myotubes from human skeletal muscle cells, insulin- and mosapride-induced GLUT4 translocation and tyrosine phosphorylation of IRS-1 were determined. Tyrosine 110-118 insulin receptor substrate 1 Homo sapiens 138-143 20363874-6 2010 Both metformin and constitutively activated AMPK enhanced phosphorylation of IRS-1 Ser794, which led to decreased IRS-1 tyrosine phosphorylation and recruitment of the p85 subunit of PI3K. Tyrosine 120-128 insulin receptor substrate 1 Homo sapiens 77-82 20363874-6 2010 Both metformin and constitutively activated AMPK enhanced phosphorylation of IRS-1 Ser794, which led to decreased IRS-1 tyrosine phosphorylation and recruitment of the p85 subunit of PI3K. Tyrosine 120-128 insulin receptor substrate 1 Homo sapiens 114-119 20363874-7 2010 Overexpression of IRS-1 S794A was associated with increased IGF-I-stimulated IRS-1 tyrosine phosphorylation, p85 association, and protein synthesis. Tyrosine 83-91 insulin receptor substrate 1 Homo sapiens 18-23 20363874-7 2010 Overexpression of IRS-1 S794A was associated with increased IGF-I-stimulated IRS-1 tyrosine phosphorylation, p85 association, and protein synthesis. Tyrosine 83-91 insulin receptor substrate 1 Homo sapiens 77-82 20208423-6 2010 The TNFalpha-induced suppression of the tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1) and Akt in 3T3-L1 adipocytes was also reversed by SAM. Tyrosine 40-48 insulin receptor substrate 1 Homo sapiens 72-100 20208423-6 2010 The TNFalpha-induced suppression of the tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1) and Akt in 3T3-L1 adipocytes was also reversed by SAM. Tyrosine 40-48 insulin receptor substrate 1 Homo sapiens 102-107 20383171-12 2010 The level of IRS-1 ser(307) phosphorylation was decreased, whereas IRS-1 tyr phosphorylation was increased notablely. Tyrosine 73-76 insulin receptor substrate 1 Homo sapiens 67-72 20071559-9 2010 Interestingly, insulin-induced tyrosine phosphorylation of Cbl and activation of TC10 were inhibited by progesterone at 10(-5) M. These results indicate that progesterone is implicated in insulin resistance during pregnancy by inhibiting the PI 3-kinase pathway at the step of 1) IRS-1 expression and 2) distal to Akt and 3) by suppressing the PI 3-kinase-independent pathway of TC10 activation by affecting Cbl phosphorylation. Tyrosine 31-39 insulin receptor substrate 1 Homo sapiens 280-302 20060191-8 2010 While insulin treatment on human skeletal muscle cell resulted in an increased tyrosine phosphorylation of IRS-1, mosapride did not have any effect. Tyrosine 79-87 insulin receptor substrate 1 Homo sapiens 107-112 19952103-7 2010 Thus, in response to insulin increases in tyrosine phosphorylation of IR and insulin receptor substrate-1, downstream signaling to protein kinase B and glycogen synthase kinase 3 (GSK3) and glucose uptake were greater in cells overexpressing PKCdelta/alpha and the PKCdelta/delta domains than in cells expressing the PKCalpha/delta domains. Tyrosine 42-50 insulin receptor substrate 1 Homo sapiens 77-105 22011639-10 2010 Insulin administration caused a significant increase in tyrosine phosphorylation of IRS-1, leading to activation of the phosphatidylinositol 3 kinase/Akt pathway in normal liver. Tyrosine 56-64 insulin receptor substrate 1 Homo sapiens 84-89 22011639-11 2010 Postburn tyrosine phosphorylation of IRS-1 was significantly impaired, associated with an inactivation of signaling molecules acting downstream of IRS-1, leading to significantly elevated transcription of glucose-6-phosphatase and significantly decreased mRNA expression of glucokinase. Tyrosine 9-17 insulin receptor substrate 1 Homo sapiens 37-42 22011639-11 2010 Postburn tyrosine phosphorylation of IRS-1 was significantly impaired, associated with an inactivation of signaling molecules acting downstream of IRS-1, leading to significantly elevated transcription of glucose-6-phosphatase and significantly decreased mRNA expression of glucokinase. Tyrosine 9-17 insulin receptor substrate 1 Homo sapiens 147-152 20018868-11 2010 Elevated O-GlcNAc also reduces phosphorylation of the PI3K p85 binding motifs (YXXM) of IRS-1 and results in a concomitant reduction in tyrosine phosphorylation of Y(608)XXM in IRS-1, one of the two main PI3K p85 binding motifs. Tyrosine 136-144 insulin receptor substrate 1 Homo sapiens 88-93 19620130-8 2009 Ins in human kidney embryonic (HEK-293) cells causes rapid accumulation of GRK2, tyrosine phosphorylation of Ins receptor substrate 1 (IRS1) and induces glucose uptake. Tyrosine 81-89 insulin receptor substrate 1 Homo sapiens 109-133 19782747-14 2010 We found that a reduction in PKCdelta protein levels reversed the TNFalpha-mediated reduction in insulin-stimulated IRS-1 Tyr phosphorylation, Akt activation, and glycogen synthesis. Tyrosine 122-125 insulin receptor substrate 1 Homo sapiens 116-121 19636223-6 2010 The mRNA expression of insulin receptor substrate (IRS)-1 in both basal and insulin-stimulated states were down-regulated in the transfected cells (72% and 52% of controls, respectively), and the insulin-stimulated IRS-1 tyrosine phosphorylation was also significantly decreased. Tyrosine 221-229 insulin receptor substrate 1 Homo sapiens 23-57 19636223-6 2010 The mRNA expression of insulin receptor substrate (IRS)-1 in both basal and insulin-stimulated states were down-regulated in the transfected cells (72% and 52% of controls, respectively), and the insulin-stimulated IRS-1 tyrosine phosphorylation was also significantly decreased. Tyrosine 221-229 insulin receptor substrate 1 Homo sapiens 215-220 19620130-8 2009 Ins in human kidney embryonic (HEK-293) cells causes rapid accumulation of GRK2, tyrosine phosphorylation of Ins receptor substrate 1 (IRS1) and induces glucose uptake. Tyrosine 81-89 insulin receptor substrate 1 Homo sapiens 135-139 19620130-10 2009 Similarly, transgenic GRK2 overexpression prevents Ins-induced tyrosine phosphorylation of IRS1 and glucose uptake, whereas GRK2-DN ameliorates glucose extraction. Tyrosine 63-71 insulin receptor substrate 1 Homo sapiens 91-95 19620130-13 2009 In SHR, Ant-124 infusion for 30 days ameliorates IRES and IRS1 tyrosine phosphorylation. Tyrosine 63-71 insulin receptor substrate 1 Homo sapiens 58-62 19762915-4 2009 In normal human chondrocytes, IGF-I initiated a strong and sustained phosphorylation of IRS-1 (Tyr-612) and Akt (Ser-473) and transient ERK phosphorylation. Tyrosine 95-98 insulin receptor substrate 1 Homo sapiens 88-93 19910497-5 2009 LAR reduces tyrosine phosphorylation of the insulin receptor, in turn leading to decreased phosphorylation of the adaptor protein IRS-1 and its downstream molecule Akt (also known as PKB). Tyrosine 12-20 insulin receptor substrate 1 Homo sapiens 130-135 19079291-8 2009 It also diminished insulin-stimulated tyrosine phosphorylation of IRS-1 and serine phosphorylation of Akt without affecting the phosphorylation of IR, ERK1/2, p38, and JNK. Tyrosine 38-46 insulin receptor substrate 1 Homo sapiens 66-71 19762915-6 2009 In normal human chondrocytes, tBHP triggered strong IRS-1 (Ser-312 and Ser-616) and ERK phosphorylation and inhibited IGF-I-induced IRS-1 (Tyr-612) and Akt phosphorylation. Tyrosine 139-142 insulin receptor substrate 1 Homo sapiens 132-137 19724894-4 2009 These studies demonstrated that there is a dramatic change in the phosphorylation pattern of Tyr, Ser and Thr residues in IRS-1 as a function of insulin levels. Tyrosine 93-96 insulin receptor substrate 1 Homo sapiens 122-127 19781106-8 2009 Assessment of skeletal muscle insulin signaling demonstrated increased tyrosine phosphorylation of IRS-1 (p < 0.001) and increased IRS-1-associated phosphatidylinositol 3 (PI 3)-kinase activity (p < 0.001) following HC overfeeding. Tyrosine 71-79 insulin receptor substrate 1 Homo sapiens 99-104 19738073-2 2009 TGF-beta1-induced EMT and cell migration in A549 cells are associated with a decrease in IRS-1 tyrosine phosphorylation and protein levels. Tyrosine 95-103 insulin receptor substrate 1 Homo sapiens 89-94 19738073-7 2009 Inhibition of protein tyrosine phosphatase with sodium vanadate, which greatly increased the levels of tyrosine-phosphorylated IRS-1, suppressed TGF-beta1-induced actin remodeling and cell morphologic changes. Tyrosine 22-30 insulin receptor substrate 1 Homo sapiens 127-132 19523477-3 2009 We found that cholesterol treatment produces robust insulin signaling resistance that is characterized by the marked reduction in insulin-stimulated tyrosine phosphorylation of the IR and its downstream targets insulin receptor substrate 1 (IRS1) and 2 (IRS2). Tyrosine 149-157 insulin receptor substrate 1 Homo sapiens 211-239 19523477-3 2009 We found that cholesterol treatment produces robust insulin signaling resistance that is characterized by the marked reduction in insulin-stimulated tyrosine phosphorylation of the IR and its downstream targets insulin receptor substrate 1 (IRS1) and 2 (IRS2). Tyrosine 149-157 insulin receptor substrate 1 Homo sapiens 241-245 19593406-6 2009 Similarly to the situation in T2D subjects, in subjects on the high-calorie diet, the amount of insulin receptors was reduced and phosphorylation of IRS1 at tyrosine and at serine-307 (human sequence, corresponding to murine serine-302) were impaired. Tyrosine 157-165 insulin receptor substrate 1 Homo sapiens 149-153 19103747-6 2009 This was accompanied by increased phosphorylation of JNK and serine phosphorylation of insulin receptor substrate 1 (IRS-1), along with inhibition of insulin signaling steps, such as tyrosine phosphorylation of IRS-1, and phosphorylation of Akt and ERK. Tyrosine 183-191 insulin receptor substrate 1 Homo sapiens 211-216 19596798-6 2009 During cilium formation, insulin receptor substrate 1 (IRS-1), one of the important downstream signaling molecules of the IGF-1 receptor, was recruited to the basal body at which it was phosphorylated on tyrosine by the receptor kinase in cilia. Tyrosine 204-212 insulin receptor substrate 1 Homo sapiens 25-53 19596798-6 2009 During cilium formation, insulin receptor substrate 1 (IRS-1), one of the important downstream signaling molecules of the IGF-1 receptor, was recruited to the basal body at which it was phosphorylated on tyrosine by the receptor kinase in cilia. Tyrosine 204-212 insulin receptor substrate 1 Homo sapiens 55-60 19164446-1 2009 Insulin receptor substrate-1 (IRS-1) is a docking protein tyrosine phosphorylated in response to insulin, IGF-1, GH, and other cytokines. Tyrosine 58-66 insulin receptor substrate 1 Homo sapiens 0-28 19164446-1 2009 Insulin receptor substrate-1 (IRS-1) is a docking protein tyrosine phosphorylated in response to insulin, IGF-1, GH, and other cytokines. Tyrosine 58-66 insulin receptor substrate 1 Homo sapiens 30-35 19164446-2 2009 IRS-1 has an N-terminal plekstrin homology domain (which facilitates membrane localization), a phosphotyrosine-binding domain [which associates with tyrosine-phosphorylated insulin receptor or IGF-1 receptor (IGF-1R)], and tyrosine residues that, when phosphorylated, bind signaling molecules. Tyrosine 102-110 insulin receptor substrate 1 Homo sapiens 0-5 19164446-2 2009 IRS-1 has an N-terminal plekstrin homology domain (which facilitates membrane localization), a phosphotyrosine-binding domain [which associates with tyrosine-phosphorylated insulin receptor or IGF-1 receptor (IGF-1R)], and tyrosine residues that, when phosphorylated, bind signaling molecules. Tyrosine 149-157 insulin receptor substrate 1 Homo sapiens 0-5 19348241-1 2009 Angiotensin II suppresses the insulin sensitivity via enhancement of serine phosphorylation of insulin receptor and suppression of tyrosine phosphorylation of IRS-1. Tyrosine 131-139 insulin receptor substrate 1 Homo sapiens 159-164 19381127-2 2009 Both events inhibit insulin receptor and IRS-1 (insulin receptor substrate) tyrosine phosphorylation. Tyrosine 76-84 insulin receptor substrate 1 Homo sapiens 41-46 18663085-4 2008 METHODS AND RESULTS: ApoCIII inhibited insulin-induced tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1), decreasing phosphatidylinositol 3-kinase (PI3K)/Akt activation in human umbilical vein endothelial cells. Tyrosine 55-63 insulin receptor substrate 1 Homo sapiens 113-118 18687633-8 2008 These data suggest that a higher proportion of the EGFR mutant carcinoma cells may exhibit activation of the phosphatidylinositol 3-kinase/protein kinase B (AKT)/mammalian target of rapamycin (MTOR) pathway through Tyr-1148 and Tyr-1068 and suppression of IRS-1 Ser-612, altered heterodimerization with ERBB2, reduced response to transforming growth factor beta suppression, and reduced ubiquitination/degradation of the EGFR through EGFR Tyr-1045, thus providing a survival advantage. Tyrosine 215-218 insulin receptor substrate 1 Homo sapiens 256-261 17902048-2 2008 Here, however, we show that in tamoxifen-resistant MCF-7 (Tam-R) breast cancer cells, that are highly dependent on epidermal growth factor receptor (EGFR) for growth, IRS-1 can interact with EGFR and be preferentially phosphorylated on tyrosine (Y) 896, a Grb2 binding site. Tyrosine 236-244 insulin receptor substrate 1 Homo sapiens 167-172 18495085-1 2008 Previous study showed that Trichostatin A (TSA) could improve insulin receptor substrate 1 (IRS-1) phosphorylation at tyrosine in response to insulin evocation. Tyrosine 118-126 insulin receptor substrate 1 Homo sapiens 62-90 18495085-1 2008 Previous study showed that Trichostatin A (TSA) could improve insulin receptor substrate 1 (IRS-1) phosphorylation at tyrosine in response to insulin evocation. Tyrosine 118-126 insulin receptor substrate 1 Homo sapiens 92-97 18420488-10 2008 In fact, Ad-36 decreased insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation and IRS-1-and IRS-2-associated PI 3-kinase activities. Tyrosine 62-70 insulin receptor substrate 1 Homo sapiens 25-53 18792873-8 2008 Further, AGEs decreased tyrosine phosphorylation of IRS-1, and subsequently reduced the association of p85 subunit of phosphatidylinositol 3-kinase with IRS-1 and glycogen synthesis in insulin-exposed Hep3B cells, all of which were inhibited by PEDF. Tyrosine 24-32 insulin receptor substrate 1 Homo sapiens 52-57 18420488-10 2008 In fact, Ad-36 decreased insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation and IRS-1-and IRS-2-associated PI 3-kinase activities. Tyrosine 62-70 insulin receptor substrate 1 Homo sapiens 55-60 18207474-6 2008 DAG is identified as a potential mediator of lipid-induced insulin resistance, as increased DAG levels are associated with protein kinase C activation and a reduction in both insulin-stimulated IRS-1 tyrosine phosphorylation and PI3 kinase activity. Tyrosine 200-208 insulin receptor substrate 1 Homo sapiens 194-199 18314420-10 2008 In contrast, insulin action on IRS-1 tyrosine phosphorylation, tyrosine-associated phosphatidylinositol (PI) 3-kinase activity, Akt, and glycogen synthase kinase (GSK) phosphorylation was unaltered between myotubes transfected with siRNA against MCD versus a scrambled sequence. Tyrosine 37-45 insulin receptor substrate 1 Homo sapiens 31-36 18064649-6 2008 We also show that IRS-1 binds to src via its two PI3-K binding tyrosine residues, and that these two residues are required for transformation of mammary cancer cells expressing v-src. Tyrosine 63-71 insulin receptor substrate 1 Homo sapiens 18-23 19035139-1 2008 OBJECTIVE: To investigate the mRNA, protein expression and tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) in endometrial carcinoma. Tyrosine 59-67 insulin receptor substrate 1 Homo sapiens 87-115 19035139-1 2008 OBJECTIVE: To investigate the mRNA, protein expression and tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) in endometrial carcinoma. Tyrosine 59-67 insulin receptor substrate 1 Homo sapiens 117-122 19035139-6 2008 Immunoprecipitation was used to measure the tyrosine phosphorylation of IRS-1. Tyrosine 44-52 insulin receptor substrate 1 Homo sapiens 72-77 19035139-9 2008 Tyrosine phosphorylation of IRS-1 in EC group [(62 +/- 36) %] was higher than that in AHE and NE groups [(53 +/-34)% and (35 +/- 33)%; P=0.048, 0.002]. Tyrosine 0-8 insulin receptor substrate 1 Homo sapiens 28-33 19035139-12 2008 IRS-1 tyrosine phosphorylation was significantly higher in patients with advanced stage, high grade, deep myometrial invasion and pelvic lymph node metastasis. Tyrosine 6-14 insulin receptor substrate 1 Homo sapiens 0-5 18174527-8 2008 Moreover, FALDH, by reducing adduct formation, partially restores HNE-generated decrease in insulin-induced IRS-1 tyrosine phosphorylation and metabolic responses. Tyrosine 114-122 insulin receptor substrate 1 Homo sapiens 108-113 18469500-7 2008 Insulin-induced tyrosine phosphorylation of IRS-1 and serine/threonine phosphorylation of Akt were reduced by atorvastatin. Tyrosine 16-24 insulin receptor substrate 1 Homo sapiens 44-49 18252807-4 2008 Consequently, this allowed cells to restore insulin signals, which was evidenced by decrease in the ratio of serine to tyrosine phosphorylations of IRS1 and increase in the phosphorylations of Akt and glycogen synthase kinase (GSK) 3beta. Tyrosine 119-127 insulin receptor substrate 1 Homo sapiens 148-152 17709744-4 2007 Here we show that S6K1 directly phosphorylates IRS-1 Ser-1101 in vitro in the C-terminal domain of the protein and that mutation of this site largely blocks the ability of amino acids to suppress IRS-1 tyrosine and Akt phosphorylation. Tyrosine 202-210 insulin receptor substrate 1 Homo sapiens 47-52 17711920-9 2007 In addition, whereas insulin receptor substrate (IRS)-1 protein expression did not change, IRS-1 tyrosine phosphorylation increased. Tyrosine 97-105 insulin receptor substrate 1 Homo sapiens 91-96 17640984-1 2007 The function of insulin receptor substrate-1 (IRS-1) is regulated by both tyrosine and serine/threonine phosphorylation. Tyrosine 74-82 insulin receptor substrate 1 Homo sapiens 16-44 17640984-1 2007 The function of insulin receptor substrate-1 (IRS-1) is regulated by both tyrosine and serine/threonine phosphorylation. Tyrosine 74-82 insulin receptor substrate 1 Homo sapiens 46-51 18380932-3 2008 It also decreased tyrosine phosphorylation of IRS-1 and, subsequently, reduced the association of the p85 subunit of phosphatidylinositol 3-kinase with IRS-1 and glycogen synthesis in insulin-exposed Hep3B cells, all of which were inhibited by telmisartan. Tyrosine 18-26 insulin receptor substrate 1 Homo sapiens 46-51 18036576-8 2008 IL-1beta reduced tyrosine phosphorylation of the docking proteins, IRS-1 and Shc, which convey receptor activation to the downstream protein kinase cascades. Tyrosine 17-25 insulin receptor substrate 1 Homo sapiens 67-72 17965023-6 2007 In CHO-C400 cells, expression of 53BP2S reduced insulin-stimulated IRS-1 tyrosine phosphorylation with a concomitant enhancement of IRS-2 tyrosine phosphorylation. Tyrosine 73-81 insulin receptor substrate 1 Homo sapiens 67-72 17827393-5 2007 Furthermore, IGF-1 stimulates tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and IRS-2 and their association with the p85 subunit of phosphoinositide-3 kinase (PI3K). Tyrosine 30-38 insulin receptor substrate 1 Homo sapiens 58-86 17827393-5 2007 Furthermore, IGF-1 stimulates tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and IRS-2 and their association with the p85 subunit of phosphoinositide-3 kinase (PI3K). Tyrosine 30-38 insulin receptor substrate 1 Homo sapiens 88-93 17827393-6 2007 IGF-1-stimulated tyrosine phosphorylation of IRS-1 and IRS-2 and subsequent p85 binding is transient and precedes phosphorylation of protein kinase B (PKB) on Ser473. Tyrosine 17-25 insulin receptor substrate 1 Homo sapiens 45-50 17868644-4 2007 ER stress, in turn, leads to the suppression of insulin receptor signaling through tyrosine dephosphorylation of IRS-1. Tyrosine 83-91 insulin receptor substrate 1 Homo sapiens 113-118 17565041-9 2007 Overexpression of SH2B1 enhanced both JAK2- and JAK2(Y813F)-mediated tyrosine phosphorylation of IRS1 in response to leptin, even though SH2B1 did not enhance JAK2(Y813F) activation. Tyrosine 69-77 insulin receptor substrate 1 Homo sapiens 97-101 17709744-4 2007 Here we show that S6K1 directly phosphorylates IRS-1 Ser-1101 in vitro in the C-terminal domain of the protein and that mutation of this site largely blocks the ability of amino acids to suppress IRS-1 tyrosine and Akt phosphorylation. Tyrosine 202-210 insulin receptor substrate 1 Homo sapiens 196-201 17712722-6 2007 The induction of CCAAT/enhancer binding protein alpha was reduced by 37% (p<0.05), correlating with a similar reduction in insulin-stimulated IRS-1 tyrosine phosphorylation and glucose transport in DDR2-L1 adipocytes (decreases of 22% and 27%, respectively; p<0.05 for both). Tyrosine 151-159 insulin receptor substrate 1 Homo sapiens 145-150 17204522-8 2007 Levels of Ser(312)-phosphorylated IRS-1 in PCOS women before LOE were higher than in controls and decreased significantly after LOE, whereas IRS-1 tyrosine phosphorylation in PCOS women before LOE was lower than in controls and increased significantly after LOE. Tyrosine 147-155 insulin receptor substrate 1 Homo sapiens 141-146 17360977-2 2007 Tyrosine phosphorylation of IRS-1 initiates insulin signaling, whereas serine/threonine phosphorylation alters the ability of IRS-1 to transduce the insulin signal. Tyrosine 0-8 insulin receptor substrate 1 Homo sapiens 28-33 17379643-4 2007 TNFalpha transiently stimulated serine phosphorylation of IRS-1 from 10 min to 1 h, whereas insulin-stimulated IRS-1 tyrosine phosphorylation was inhibited only after TNFalpha treatment longer than 4 h. These results suggest that serine phosphorylation of IRS-1 alone is not the major mechanism for the inhibited insulin signaling by TNFalpha. Tyrosine 117-125 insulin receptor substrate 1 Homo sapiens 111-116 17379643-4 2007 TNFalpha transiently stimulated serine phosphorylation of IRS-1 from 10 min to 1 h, whereas insulin-stimulated IRS-1 tyrosine phosphorylation was inhibited only after TNFalpha treatment longer than 4 h. These results suggest that serine phosphorylation of IRS-1 alone is not the major mechanism for the inhibited insulin signaling by TNFalpha. Tyrosine 117-125 insulin receptor substrate 1 Homo sapiens 111-116 17384440-8 2007 Furthermore, a prolonged exposure of hepatocytes to oleate decreased insulin-induced tyrosine phosphorylation of IRS1/2, while slightly increasing serine phosphorylation of IRS. Tyrosine 85-93 insulin receptor substrate 1 Homo sapiens 113-119 17384440-9 2007 The decrease of insulin-stimulated tyrosine phosphorylation of IRS1/2 in hepatocytes by oleate was reversed by the inhibition of p38. Tyrosine 35-43 insulin receptor substrate 1 Homo sapiens 63-69 17279354-8 2007 Exposure of L6 myotubes to hrCRP reduced insulin-stimulated phosphorylation of IRS-1 at Tyr(632), a site essential for engaging p85 subunit of phosphatidylinositol-3 kinase (PI-3K), protein kinase B (Akt) activation and glycogen synthase kinase-3 (GSK-3) phosphorylation. Tyrosine 88-91 insulin receptor substrate 1 Homo sapiens 79-84 17631765-0 2007 [Relationship between tyrosine phosphorylation and protein expression of insulin receptor substrate-1 and insulin resistance in gestational diabetes mellitus]. Tyrosine 22-30 insulin receptor substrate 1 Homo sapiens 73-101 17631765-1 2007 OBJECTIVE: To study the relationship between tyrosine phosphorylation (TP) and protein expression of insulin receptor substrate-1 (IRS-1) and insulin resistance in patients with gestational diabetes mellitus (GDM). Tyrosine 45-53 insulin receptor substrate 1 Homo sapiens 101-129 17631765-1 2007 OBJECTIVE: To study the relationship between tyrosine phosphorylation (TP) and protein expression of insulin receptor substrate-1 (IRS-1) and insulin resistance in patients with gestational diabetes mellitus (GDM). Tyrosine 45-53 insulin receptor substrate 1 Homo sapiens 131-136 17631765-10 2007 CONCLUSION: Changes in protein expression and tyrosine phosphorylation of IRS-1 in skeletal muscle may be one of the molecular mechanisms leading to insulin resistance in patients with GDM. Tyrosine 46-54 insulin receptor substrate 1 Homo sapiens 74-79 17179152-7 2007 Protein tyrosine phosphatases (PTPs) appear to be important for the IRS-1 cleavage because tyrosine phosphorylation of the insulin receptor was decreased in hypoxia and IRS-1 cleavage could be blocked either with H(2)O(2) or with vanadate, each of which inhibits PTPs. Tyrosine 8-16 insulin receptor substrate 1 Homo sapiens 68-73 17244624-2 2007 We found that treating C2C12 myotubes with adiponectin or rapamycin enhanced the ability of insulin to stimulate IRS-1 tyrosine phosphorylation and Akt phosphorylation, concurrently with reduced p70 S6 kinase phosphorylation at Thr389 as well as IRS-1 phosphorylation at Ser302 and Ser636/639. Tyrosine 119-127 insulin receptor substrate 1 Homo sapiens 113-118 17179152-7 2007 Protein tyrosine phosphatases (PTPs) appear to be important for the IRS-1 cleavage because tyrosine phosphorylation of the insulin receptor was decreased in hypoxia and IRS-1 cleavage could be blocked either with H(2)O(2) or with vanadate, each of which inhibits PTPs. Tyrosine 8-16 insulin receptor substrate 1 Homo sapiens 169-174 16644673-5 2006 TNF-alpha significantly activated ASK1, increased serine phosphorylation of insulin receptor substrate (IRS)-1, and decreased insulin-stimulated tyrosine phosphorylation of IRS-1 and serine phosphorylation of Akt, and all of these effects were inhibited by overexpression of either UCP-1 or MnSOD. Tyrosine 145-153 insulin receptor substrate 1 Homo sapiens 173-178 17242212-5 2007 In addition, IL-6 treatment resulted in impaired IRS-1 phosphorylation at Tyr(612), a site essential for engaging PI3-kinase. Tyrosine 74-77 insulin receptor substrate 1 Homo sapiens 49-54 16960657-5 2007 While chronic exposure to OHB did not alter insulin- or vanadate-mediated activation of the insulin receptor, it suppressed insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation in response to both agonists. Tyrosine 161-169 insulin receptor substrate 1 Homo sapiens 124-152 16960657-5 2007 While chronic exposure to OHB did not alter insulin- or vanadate-mediated activation of the insulin receptor, it suppressed insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation in response to both agonists. Tyrosine 161-169 insulin receptor substrate 1 Homo sapiens 154-159 16982630-6 2006 Furthermore, Ang II abolished insulin-induced tyrosine phosphorylation of insulin receptor substrate 1 (IRS1), activation of protein kinase B (Akt), and glucose transporter-4 (GLUT4) translocation to the plasma membrane, which was reversed by pretreating myotubes with losartan or apocynin. Tyrosine 46-54 insulin receptor substrate 1 Homo sapiens 74-102 16982630-6 2006 Furthermore, Ang II abolished insulin-induced tyrosine phosphorylation of insulin receptor substrate 1 (IRS1), activation of protein kinase B (Akt), and glucose transporter-4 (GLUT4) translocation to the plasma membrane, which was reversed by pretreating myotubes with losartan or apocynin. Tyrosine 46-54 insulin receptor substrate 1 Homo sapiens 104-108 16970908-1 2006 The IRS-1 PH and PTB domains are essential for insulin-stimulated IRS-1 Tyr phosphorylation and insulin signaling, while Ser/Thr phosphorylation of IRS-1 disrupts these signaling events. Tyrosine 72-75 insulin receptor substrate 1 Homo sapiens 4-9 16970908-1 2006 The IRS-1 PH and PTB domains are essential for insulin-stimulated IRS-1 Tyr phosphorylation and insulin signaling, while Ser/Thr phosphorylation of IRS-1 disrupts these signaling events. Tyrosine 72-75 insulin receptor substrate 1 Homo sapiens 66-71 16970908-1 2006 The IRS-1 PH and PTB domains are essential for insulin-stimulated IRS-1 Tyr phosphorylation and insulin signaling, while Ser/Thr phosphorylation of IRS-1 disrupts these signaling events. Tyrosine 72-75 insulin receptor substrate 1 Homo sapiens 66-71 16970908-3 2006 The 3A mutant abrogated the inhibitory effect of PKCdelta on insulin-stimulated IRS-1 Tyr phosphorylation, while reductions in insulin-stimulated IRS-1 Tyr phosphorylation, cellular proliferation, and Akt activation were observed with the 3E mutant. Tyrosine 86-89 insulin receptor substrate 1 Homo sapiens 80-85 16970908-4 2006 When single Glu mutants were tested, the Ser24 to Glu mutant had the greatest inhibitory effect on insulin-stimulated IRS-1 Tyr phosphorylation. Tyrosine 124-127 insulin receptor substrate 1 Homo sapiens 118-123 17038556-9 2007 The decrease in IRS-1 amount resulted in a reduction in its tyrosine phosphorylation and the alteration of insulin-induced protein kinase B activation and AS160 phosphorylation. Tyrosine 60-68 insulin receptor substrate 1 Homo sapiens 16-21 17986823-3 2007 One early molecular event that links the receptor kinase to the biologic actions of IGF-1 is tyrosine phosphorylation of the insulin receptor substrate family (IRS-1 to -4). Tyrosine 93-101 insulin receptor substrate 1 Homo sapiens 160-171 17986823-5 2007 Phosphorylation of multiple tyrosine residues results in the association of IRS-1 with the Src homology 2 (SH2) domains of other cytoplasmic signaling proteins, including phosphatidylinositol 3" kinase, Syp, Grb2 and Nck. Tyrosine 28-36 insulin receptor substrate 1 Homo sapiens 76-81 16611834-5 2006 Mutation of Ser-318 to alanine abrogates the inhibitory effect of leptin on insulin-induced Irs1 tyrosine phosphorylation and glucose uptake in L6 myoblasts. Tyrosine 97-105 insulin receptor substrate 1 Homo sapiens 92-96 16150868-4 2006 IL-1alpha treatment up to 4 h did not alter insulin-stimulated insulin receptor tyrosine phosphorylation, whereas tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and the association with phosphatidylinositol 3-kinase were partially inhibited with the maximal inhibition in around 15 min. Tyrosine 114-122 insulin receptor substrate 1 Homo sapiens 142-176 16306077-7 2006 Substitution for these tyrosines in p85 resulted in loss of SHP-2 recruitment and was associated with a reduction in association of the p85/p110 complex with insulin receptor substrate-1. Tyrosine 23-32 insulin receptor substrate 1 Homo sapiens 158-186 16622294-4 2006 Weight loss and thiazolidinediones (TZDs) improve glucose disposal, in part, by increasing insulin-stimulated insulin receptor and IRS-1 tyrosine phosphorylation and PI 3-kinase activity. Tyrosine 137-145 insulin receptor substrate 1 Homo sapiens 131-136 16150868-7 2006 Tyrosine phosphorylation of IRS-1 was recovered only by the IKK inhibitor or JNK inhibitor, suggesting specific involvement of these two kinases. Tyrosine 0-8 insulin receptor substrate 1 Homo sapiens 28-33 16235045-4 2005 Each of the three VO2+ chelates increased the tyrosine phosphorylation of proteins in response to insulin, including the beta-subunit of the insulin receptor (IRbeta) and the insulin receptor substrate-1 (IRS1). Tyrosine 46-54 insulin receptor substrate 1 Homo sapiens 175-203 16128672-3 2005 Attention has focused on early signalling events such as defective tyrosine phosphorylation of IRS1 (insulin receptor substrate-1), a major target for the insulin receptor tyrosine kinase. Tyrosine 67-75 insulin receptor substrate 1 Homo sapiens 95-99 16128672-3 2005 Attention has focused on early signalling events such as defective tyrosine phosphorylation of IRS1 (insulin receptor substrate-1), a major target for the insulin receptor tyrosine kinase. Tyrosine 67-75 insulin receptor substrate 1 Homo sapiens 101-129 16130009-7 2005 Within the insulin-signaling cascade IRS-1 tyrosine phosphorylation was induced several fold by insulin and was diminished by preincubation with olanzapine. Tyrosine 43-51 insulin receptor substrate 1 Homo sapiens 37-42 16235045-4 2005 Each of the three VO2+ chelates increased the tyrosine phosphorylation of proteins in response to insulin, including the beta-subunit of the insulin receptor (IRbeta) and the insulin receptor substrate-1 (IRS1). Tyrosine 46-54 insulin receptor substrate 1 Homo sapiens 205-209 16129690-4 2005 Inhibition of serine 307 phosphorylation by rapamycin mimicked type 2 diabetes and reduced the sensitivity of IRS1 tyrosine phosphorylation in response to insulin, while stimulation of the phosphorylation by okadaic acid, in cells from patients with type 2 diabetes, rescued cells from insulin resistance. Tyrosine 115-123 insulin receptor substrate 1 Homo sapiens 110-114 15994203-3 2005 We have also reported that chronic endothelin-1 (ET-1) treatment leads to heterologous desensitization of insulin signaling with decreased tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and Galphaq/11, and decreased insulin-stimulated glucose transport in 3T3-L1 adipocytes. Tyrosine 139-147 insulin receptor substrate 1 Homo sapiens 167-201 16020478-10 2005 These data suggest that phosphorylation of Ser1223 dampens association of IRS-1 with SHP-2, thereby increasing net insulin-stimulated tyrosine phosphorylation. Tyrosine 134-142 insulin receptor substrate 1 Homo sapiens 74-79 15952796-7 2005 Replacing Ser(150) and Ser(476) with alanines reduced the inhibitory effect of human Grb10zeta on insulin-stimulated IRS1 tyrosine phosphorylation. Tyrosine 122-130 insulin receptor substrate 1 Homo sapiens 117-121 16093437-2 2005 On ligand stimulation, IGF-IR, a receptor tyrosine kinase, phosphorylates tyrosine residues on two major substrates, IRS-1 and Shc, which subsequently signal through the Ras/mitogen-activated protein kinase and phosphatidylinositol 3-kinase/AKT pathways. Tyrosine 42-50 insulin receptor substrate 1 Homo sapiens 117-122 16248779-3 2005 Effects are mediated through a variety of mechanisms that include attenuation of key insulin signalling pathways and decreased tyrosine phosphorylation of insulin receptor substrates IRS-1, SHC and G alpha q/11. Tyrosine 127-135 insulin receptor substrate 1 Homo sapiens 183-188 16046301-4 2005 Increased basal phosphorylation of Ser307 IRS-1 in the obese and type 2 diabetic subjects corresponds with decrease in insulin-stimulated IRS-1 tyrosine phosphorylation, PI 3-kinase activity, and insulin-induced activation of Akt and, more prominently, PKC-zeta/lambda. Tyrosine 144-152 insulin receptor substrate 1 Homo sapiens 42-47 16046301-4 2005 Increased basal phosphorylation of Ser307 IRS-1 in the obese and type 2 diabetic subjects corresponds with decrease in insulin-stimulated IRS-1 tyrosine phosphorylation, PI 3-kinase activity, and insulin-induced activation of Akt and, more prominently, PKC-zeta/lambda. Tyrosine 144-152 insulin receptor substrate 1 Homo sapiens 138-143 15924436-7 2005 Purified plasma membranes exhibited insulin-dependent kinase activity in assays using substrate peptides mimicking sites of Tyr phosphorylation in the endogenous substrate IRS-1. Tyrosine 124-127 insulin receptor substrate 1 Homo sapiens 172-177 15929863-3 2005 Fatty acids appear to cause this defect in glucose transport by inhibiting insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and IRS-1-associated phosphatidylinositol 3-kinase activity. Tyrosine 94-102 insulin receptor substrate 1 Homo sapiens 152-157 15713122-1 2005 Serine and threonine phosphorylation of IRS-1 (insulin receptor substrate-1) has been reported to decrease its ability to be tyrosine-phosphorylated by the insulin receptor. Tyrosine 125-133 insulin receptor substrate 1 Homo sapiens 40-45 15713122-1 2005 Serine and threonine phosphorylation of IRS-1 (insulin receptor substrate-1) has been reported to decrease its ability to be tyrosine-phosphorylated by the insulin receptor. Tyrosine 125-133 insulin receptor substrate 1 Homo sapiens 47-75 15713122-2 2005 Insulin itself may negatively regulate tyrosine phosphorylation of IRS-1 through a PI3K (phosphoinositide 3-kinase)-dependent feedback pathway. Tyrosine 39-47 insulin receptor substrate 1 Homo sapiens 67-72 15713122-3 2005 In the present study, we examined the regulation and role of IRS-1 serine phosphorylation in the modulation of IRS-1 tyrosine phosphorylation in physiologically relevant cells, namely freshly isolated primary adipocytes. Tyrosine 117-125 insulin receptor substrate 1 Homo sapiens 61-66 15713122-3 2005 In the present study, we examined the regulation and role of IRS-1 serine phosphorylation in the modulation of IRS-1 tyrosine phosphorylation in physiologically relevant cells, namely freshly isolated primary adipocytes. Tyrosine 117-125 insulin receptor substrate 1 Homo sapiens 111-116 15713122-8 2005 The differential effect of inhibition of ERK1/2 on insulin-stimulated IRS-1 phosphorylation of Ser312/Ser616 and tyrosine indicates that these events are independent of each other and that phosphorylation of Ser312/Ser616 is not responsible for the negative regulation of IRS-1 tyrosine phosphorylation mediated by PI3K in primary adipocytes. Tyrosine 113-121 insulin receptor substrate 1 Homo sapiens 70-75 15713122-8 2005 The differential effect of inhibition of ERK1/2 on insulin-stimulated IRS-1 phosphorylation of Ser312/Ser616 and tyrosine indicates that these events are independent of each other and that phosphorylation of Ser312/Ser616 is not responsible for the negative regulation of IRS-1 tyrosine phosphorylation mediated by PI3K in primary adipocytes. Tyrosine 278-286 insulin receptor substrate 1 Homo sapiens 70-75 15870194-9 2005 Because tyrosine phosphorylation of IRS-1 activates the insulin signaling pathway and serine phosphorylation of IRS-1 blocks insulin action, our findings that insulin increases BVR tyrosine phosphorylation and that there is an increase in glucose uptake in response to insulin when expression of BVR is "knocked down" by small interfering RNA suggest a potential role for BVR in the insulin signaling pathway. Tyrosine 8-16 insulin receptor substrate 1 Homo sapiens 36-41 15855334-4 2005 Insulin increased insulin receptor substrate 1 (IRS-1) tyrosine phosphorylation, IRS-1-associated phosphatidylinositol (PI) 3-kinase activity, and phosphorylation of Akt Ser473 and AS160, a newly described Akt substrate that plays a role in GLUT4 exocytosis, approximately 2.3 fold before treatment. Tyrosine 55-63 insulin receptor substrate 1 Homo sapiens 48-53 15824195-3 2005 Fatty acids appear to cause this defect in glucose transport by inhibiting insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and IRS-1 associated phosphatidylinositol 3-kinase activity. Tyrosine 94-102 insulin receptor substrate 1 Homo sapiens 152-157 15870194-9 2005 Because tyrosine phosphorylation of IRS-1 activates the insulin signaling pathway and serine phosphorylation of IRS-1 blocks insulin action, our findings that insulin increases BVR tyrosine phosphorylation and that there is an increase in glucose uptake in response to insulin when expression of BVR is "knocked down" by small interfering RNA suggest a potential role for BVR in the insulin signaling pathway. Tyrosine 181-189 insulin receptor substrate 1 Homo sapiens 112-117 15699039-6 2005 We measured insulin receptor amount and insulin-dependent receptor autophosphorylation as well as insulin receptor substrate 1 (IRS1) tyrosine phosphorylation as an index of insulin signaling. Tyrosine 134-142 insulin receptor substrate 1 Homo sapiens 128-132 15699039-8 2005 Likewise, we determined that insulin-dependent insulin receptor and IRS1 tyrosine phosphorylation was not significantly different in the four cell lines representing parental, low, medium, and high levels of caveolin-1 expression. Tyrosine 73-81 insulin receptor substrate 1 Homo sapiens 68-72 15721320-5 2005 Here, we identify the death domain of TNF-R55 as responsible for the inhibitory effects of TNF on tyrosine phosphorylation of IRS-1, implicating ceramide generated by A-SMase as a downstream mediator of inhibition of IR signaling. Tyrosine 98-106 insulin receptor substrate 1 Homo sapiens 126-131 15747109-5 2005 Insulin-stimulated tyrosine phosphorylation of IRS-1, and IRS-1- and IRS-2-associated phosphatidylinositol 3-kinase (PI3K) activity were not impaired by TGRLs, suggesting that these steps were not involved in the lipoprotein-induced effects on glucose metabolism. Tyrosine 19-27 insulin receptor substrate 1 Homo sapiens 47-52 15840294-4 2005 IRS-1 tyrosine phosphorylation in adipose tissue in the obese PCOS group [(52 +/- 23)%, P < 0.001], the obese control group [(45 +/- 22)%, P < 0.01] and non-obese PCOS group [(70 +/- 25)%, P < 0.05] were markedly lower than that in the non-obese control group (88 +/- 12)%. Tyrosine 6-14 insulin receptor substrate 1 Homo sapiens 0-5 15777207-5 2005 The insulin-like effects are mediated by the cytosolic tyrosine kinase Janus kinase 2 (JAK2) upon GH-GH receptor interaction, resulting in tyrosine phosphorylation of downstream targets including the GH receptor itself and insulin receptor substrate-1 (IRS-1) and IRS-2. Tyrosine 55-63 insulin receptor substrate 1 Homo sapiens 223-251 15777207-5 2005 The insulin-like effects are mediated by the cytosolic tyrosine kinase Janus kinase 2 (JAK2) upon GH-GH receptor interaction, resulting in tyrosine phosphorylation of downstream targets including the GH receptor itself and insulin receptor substrate-1 (IRS-1) and IRS-2. Tyrosine 55-63 insulin receptor substrate 1 Homo sapiens 253-258 15840294-7 2005 CONCLUSION: IRS-1 tyrosine phosphorylation in adipose tissue in the two PCOS groups decreased markedly than in the non-obese control group. Tyrosine 18-26 insulin receptor substrate 1 Homo sapiens 12-17 15733744-2 2005 While the phosphorylation of IRS1 on tyrosine residue is required for insulin-stimulated responses, the phosphorylation of IRS1 on serine residues has a dual role, either to enhance or to terminate the insulin effects. Tyrosine 37-45 insulin receptor substrate 1 Homo sapiens 29-33 15606684-6 2005 At the cellular level, vanadium activates several key elements of the insulin signal transduction pathway, such as the tyrosine phosphorylation of insulin receptor substrate-1, and extracellular signal-regulated kinase 1 and 2, phosphatidylinositol 3-kinase and protein kinase B activation. Tyrosine 119-127 insulin receptor substrate 1 Homo sapiens 147-175 15364919-4 2004 Here we show that PKC phosphorylates IRS1 at serine 1101 blocking IRS1 tyrosine phosphorylation and downstream activation of the Akt pathway. Tyrosine 71-79 insulin receptor substrate 1 Homo sapiens 37-41 15634339-2 2005 Directly after surgery and cell isolation, adipocytes were insulin resistant, but this was reversed after overnight incubation in 10% CO(2) at 37 degrees C. Tyrosine phosphorylation of the insulin receptor and insulin receptor substrate (IRS)1 was insulin sensitive, but protein kinase B (PKB) and downstream metabolic effects exhibited insulin resistance that was reversed by overnight incubation. Tyrosine 157-165 insulin receptor substrate 1 Homo sapiens 189-243 15448167-8 2004 1) It strongly increased IGF-1-induced tyrosine phosphorylation of IRS-1 and IRS-1-associated phosphatidylinositol 3-kinase through activation of the epidermal growth factor receptor. Tyrosine 39-47 insulin receptor substrate 1 Homo sapiens 67-72 15364919-4 2004 Here we show that PKC phosphorylates IRS1 at serine 1101 blocking IRS1 tyrosine phosphorylation and downstream activation of the Akt pathway. Tyrosine 71-79 insulin receptor substrate 1 Homo sapiens 66-70 15161606-4 2004 Insulin receptor substrate-1 (IRS-1)-associated PI3K activity was not altered in cells acidified for 10 min but was strongly inhibited in cells incubated at pH 7.1 for 24 h. Phosphorylation of Akt was also suppressed by acidification for 24 h. Acidification did not induce changes in IRS-1 abundance, insulin-stimulated IRS-1 tyrosine phosphorylation, or the amount of PI3K p85 regulatory subunit. Tyrosine 326-334 insulin receptor substrate 1 Homo sapiens 0-28 15316008-7 2004 SH2-B mutants with lower affinity for IRS1 and IRS2 exhibited reduced ability to promote association of JAK2 with IRS1, tyrosine phosphorylation of IRS1, and association of IRS1 with p85 in response to leptin. Tyrosine 120-128 insulin receptor substrate 1 Homo sapiens 38-42 15316008-9 2004 Similarly, SH2-B promoted growth hormone-stimulated tyrosine phosphorylation of IRS1 in both HEK293 and MEF cells. Tyrosine 52-60 insulin receptor substrate 1 Homo sapiens 80-84 15161606-4 2004 Insulin receptor substrate-1 (IRS-1)-associated PI3K activity was not altered in cells acidified for 10 min but was strongly inhibited in cells incubated at pH 7.1 for 24 h. Phosphorylation of Akt was also suppressed by acidification for 24 h. Acidification did not induce changes in IRS-1 abundance, insulin-stimulated IRS-1 tyrosine phosphorylation, or the amount of PI3K p85 regulatory subunit. Tyrosine 326-334 insulin receptor substrate 1 Homo sapiens 30-35 15069075-8 2004 Moreover, we found that the previously described insulin-stimulated, PKC-zeta-mediated inhibition of the interaction of IRS-1 with the insulin receptor and the reduced tyrosine phosphorylation of IRS-1 was abrogated by mutation of IRS-1 Ser(318) to alanine. Tyrosine 168-176 insulin receptor substrate 1 Homo sapiens 120-125 15226403-4 2004 Stimulation of these cells with mAb16-39 markedly induces the tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1), Shc, and c-Cbl and also their interaction with ALK and activation of ERK1/2. Tyrosine 62-70 insulin receptor substrate 1 Homo sapiens 90-118 15226403-4 2004 Stimulation of these cells with mAb16-39 markedly induces the tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1), Shc, and c-Cbl and also their interaction with ALK and activation of ERK1/2. Tyrosine 62-70 insulin receptor substrate 1 Homo sapiens 120-125 15069075-0 2004 Protein kinase C-zeta-induced phosphorylation of Ser318 in insulin receptor substrate-1 (IRS-1) attenuates the interaction with the insulin receptor and the tyrosine phosphorylation of IRS-1. Tyrosine 157-165 insulin receptor substrate 1 Homo sapiens 59-87 15069075-0 2004 Protein kinase C-zeta-induced phosphorylation of Ser318 in insulin receptor substrate-1 (IRS-1) attenuates the interaction with the insulin receptor and the tyrosine phosphorylation of IRS-1. Tyrosine 157-165 insulin receptor substrate 1 Homo sapiens 89-94 15069075-0 2004 Protein kinase C-zeta-induced phosphorylation of Ser318 in insulin receptor substrate-1 (IRS-1) attenuates the interaction with the insulin receptor and the tyrosine phosphorylation of IRS-1. Tyrosine 157-165 insulin receptor substrate 1 Homo sapiens 185-190 15001544-4 2004 Exposure of human pancreatic islets and RIN beta-cells to glucosamine resulted in reduction in glucose- and insulin-stimulated insulin biosynthesis, which in RIN beta-cells was associated with impairment in insulin-stimulated insulin receptor substrate-1 (IRS-1) phosphorylation at Tyr(608) and Tyr(628), which are essential for engaging phosphatidylinositol 3-kinase (PI 3-kinase). Tyrosine 282-285 insulin receptor substrate 1 Homo sapiens 226-254 15001544-4 2004 Exposure of human pancreatic islets and RIN beta-cells to glucosamine resulted in reduction in glucose- and insulin-stimulated insulin biosynthesis, which in RIN beta-cells was associated with impairment in insulin-stimulated insulin receptor substrate-1 (IRS-1) phosphorylation at Tyr(608) and Tyr(628), which are essential for engaging phosphatidylinositol 3-kinase (PI 3-kinase). Tyrosine 295-298 insulin receptor substrate 1 Homo sapiens 226-254 15001544-6 2004 RIN beta-cells exposed to high glucose exhibited increased c-Jun N-terminal kinase (JNK) and ERK1/2 activity, which was associated with increased IRS-1 phosphorylation at serine (Ser)(307) and Ser(612), respectively, that inhibits coupling of IRS-1 to the insulin receptor and is upstream of the inhibition of IRS-1 tyrosine phosphorylation. Tyrosine 316-324 insulin receptor substrate 1 Homo sapiens 146-151 15169905-4 2004 Direct overexpression of SOCS-3 in liver by adenoviral-mediated gene transfer markedly decreases tyrosine phosphorylation of both IRS-1 and IRS-2, while SOCS-1 overexpression preferentially inhibits IRS-2 phosphorylation. Tyrosine 97-105 insulin receptor substrate 1 Homo sapiens 130-135 15044323-1 2004 It has been suggested that serine (Ser) phosphorylation of insulin receptor substrate-1 (IRS-1) decreases the ability of IRS-1 to be phosphorylated on tyrosine, thereby attenuating insulin signaling. Tyrosine 151-159 insulin receptor substrate 1 Homo sapiens 59-87 15044323-1 2004 It has been suggested that serine (Ser) phosphorylation of insulin receptor substrate-1 (IRS-1) decreases the ability of IRS-1 to be phosphorylated on tyrosine, thereby attenuating insulin signaling. Tyrosine 151-159 insulin receptor substrate 1 Homo sapiens 89-94 15044323-1 2004 It has been suggested that serine (Ser) phosphorylation of insulin receptor substrate-1 (IRS-1) decreases the ability of IRS-1 to be phosphorylated on tyrosine, thereby attenuating insulin signaling. Tyrosine 151-159 insulin receptor substrate 1 Homo sapiens 121-126 14769130-6 2004 Thus muscarinic receptors may inhibit insulin signalling by promoting IRS-1 tyrosine dephosphorylation and/or by uncoupling IRS-1 from the stimulated IGF-1 receptor by stimulating IRS-1 serine phosphorylation. Tyrosine 76-84 insulin receptor substrate 1 Homo sapiens 70-75 15592487-3 2004 In skeletal muscle, the increase in LC-CoA and diacylglycerol translocates and activates specific protein kinase C (PKC) isoforms, which will phosphorylate IRS-1 on serine, preventing its phosphorylation on tyrosine and association with PI3 kinase. Tyrosine 207-215 insulin receptor substrate 1 Homo sapiens 156-161 15592489-6 2004 A common characteristic observed when activating both PKC and TNFalpha/SOCS3 is the inhibition of tyrosine phosphorylation of IRS-1 and subsequently an inhibition of its activation of downstream signalling molecules. Tyrosine 98-106 insulin receptor substrate 1 Homo sapiens 126-131 15272025-6 2004 The activated SHP-2 then dephosphorylated IRS-1 Tyr(P)-895, resulting in blockade of the pathways from IRS-1/Grb2/Sos to the ERK and p38 MAPK. Tyrosine 48-51 insulin receptor substrate 1 Homo sapiens 42-47 15272025-6 2004 The activated SHP-2 then dephosphorylated IRS-1 Tyr(P)-895, resulting in blockade of the pathways from IRS-1/Grb2/Sos to the ERK and p38 MAPK. Tyrosine 48-51 insulin receptor substrate 1 Homo sapiens 103-108 15069075-8 2004 Moreover, we found that the previously described insulin-stimulated, PKC-zeta-mediated inhibition of the interaction of IRS-1 with the insulin receptor and the reduced tyrosine phosphorylation of IRS-1 was abrogated by mutation of IRS-1 Ser(318) to alanine. Tyrosine 168-176 insulin receptor substrate 1 Homo sapiens 196-201 15069075-8 2004 Moreover, we found that the previously described insulin-stimulated, PKC-zeta-mediated inhibition of the interaction of IRS-1 with the insulin receptor and the reduced tyrosine phosphorylation of IRS-1 was abrogated by mutation of IRS-1 Ser(318) to alanine. Tyrosine 168-176 insulin receptor substrate 1 Homo sapiens 196-201 15130378-1 2004 OBJECTIVE: To investigate the tyrosine phosphorylation and protein expression of insulin receptor substrate-1 in adipose tissue from patients with polycystic ovary syndrome, and explore molecular mechanisms of insulin resistance of PCOS. Tyrosine 30-38 insulin receptor substrate 1 Homo sapiens 81-109 15126563-7 2004 Our results also showed that genistein induction of IGF-IR and IRS-1 expression resulted in enhanced tyrosine phosphorylation of IGF-IR and IRS-1 on IGF-I stimulation. Tyrosine 101-109 insulin receptor substrate 1 Homo sapiens 63-68 15140184-8 2004 Moreover, IGF-1 potently induced the tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and its association with PI3 kinase while BDNF was weak in these assays. Tyrosine 37-45 insulin receptor substrate 1 Homo sapiens 65-93 15140184-8 2004 Moreover, IGF-1 potently induced the tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and its association with PI3 kinase while BDNF was weak in these assays. Tyrosine 37-45 insulin receptor substrate 1 Homo sapiens 95-100 15003536-4 2004 Here we show that also IRS1 localizes in this region where it is tyrosine phosphorylated in the presence of IGF-I. Tyrosine 65-73 insulin receptor substrate 1 Homo sapiens 23-27 15130378-8 2004 The tyrosine phosphorylation of IRS-1 was measured by immunoprecipitation. Tyrosine 4-12 insulin receptor substrate 1 Homo sapiens 32-37 15130378-11 2004 CONCLUSIONS: The signal transduction malfunction because of protein expression and tyrosine phosphorylation changes of IRS-1 in adipose tissue from polycystic ovary syndrome patients may be one of the mechanisms leading to insulin resistance. Tyrosine 83-91 insulin receptor substrate 1 Homo sapiens 119-124 14761669-2 2004 The combined use of TZDs and metformin resulted in maximum tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate-1 (IRS-1) at 12.5 microM of TZDs and 100 microM of metformin as compared to the maximum tyrosine phosphorylation of IR and IRS-1 achieved at 50 microM of TZDs or 400 microM of metformin. Tyrosine 59-67 insulin receptor substrate 1 Homo sapiens 143-148 14761669-2 2004 The combined use of TZDs and metformin resulted in maximum tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate-1 (IRS-1) at 12.5 microM of TZDs and 100 microM of metformin as compared to the maximum tyrosine phosphorylation of IR and IRS-1 achieved at 50 microM of TZDs or 400 microM of metformin. Tyrosine 59-67 insulin receptor substrate 1 Homo sapiens 263-268 14761669-2 2004 The combined use of TZDs and metformin resulted in maximum tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate-1 (IRS-1) at 12.5 microM of TZDs and 100 microM of metformin as compared to the maximum tyrosine phosphorylation of IR and IRS-1 achieved at 50 microM of TZDs or 400 microM of metformin. Tyrosine 228-236 insulin receptor substrate 1 Homo sapiens 143-148 14668342-5 2004 EN transformation is associated with constitutive tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1). Tyrosine 50-58 insulin receptor substrate 1 Homo sapiens 78-106 14583092-0 2004 Modulation of human insulin receptor substrate-1 tyrosine phosphorylation by protein kinase Cdelta. Tyrosine 49-57 insulin receptor substrate 1 Homo sapiens 20-48 14583092-1 2004 Non-esterified fatty acid (free fatty acid)-induced activation of the novel PKC (protein kinase C) isoenzymes PKCdelta and PKCtheta correlates with insulin resistance, including decreased insulin-stimulated IRS-1 (insulin receptor substrate-1) tyrosine phosphorylation and phosphoinositide 3-kinase activation, although the mechanism(s) for this resistance is not known. Tyrosine 244-252 insulin receptor substrate 1 Homo sapiens 207-212 14583092-2 2004 In the present study, we have explored the possibility of a novel PKC, PKCdelta, to modulate directly the ability of the insulin receptor kinase to tyrosine-phosphorylate IRS-1. Tyrosine 148-156 insulin receptor substrate 1 Homo sapiens 171-176 14583092-3 2004 We have found that expression of either constitutively active PKCdelta or wild-type PKCdelta followed by phorbol ester activation both inhibit insulin-stimulated IRS-1 tyrosine phosphorylation in vivo. Tyrosine 168-176 insulin receptor substrate 1 Homo sapiens 162-167 14583092-4 2004 Activated PKCdelta was also found to inhibit the IRS-1 tyrosine phosphorylation in vitro by purified insulin receptor using recombinant full-length human IRS-1 and a partial IRS-1-glutathione S-transferase-fusion protein as substrates. Tyrosine 55-63 insulin receptor substrate 1 Homo sapiens 49-54 14583092-4 2004 Activated PKCdelta was also found to inhibit the IRS-1 tyrosine phosphorylation in vitro by purified insulin receptor using recombinant full-length human IRS-1 and a partial IRS-1-glutathione S-transferase-fusion protein as substrates. Tyrosine 55-63 insulin receptor substrate 1 Homo sapiens 154-159 14583092-4 2004 Activated PKCdelta was also found to inhibit the IRS-1 tyrosine phosphorylation in vitro by purified insulin receptor using recombinant full-length human IRS-1 and a partial IRS-1-glutathione S-transferase-fusion protein as substrates. Tyrosine 55-63 insulin receptor substrate 1 Homo sapiens 154-159 14583092-7 2004 The importance of three of the PKCdelta phosphorylation sites in IRS-1 was shown in vitro by a 75-80% decrease in the incorporation of phosphate into an IRS-1 triple mutant in which Ser-307, Ser-323 and Ser-574 were replaced by Ala. More importantly, the mutation of these three sites completely abrogated the inhibitory effect of PKCdelta on IRS-1 tyrosine phosphorylation in vitro. Tyrosine 349-357 insulin receptor substrate 1 Homo sapiens 65-70 14583092-7 2004 The importance of three of the PKCdelta phosphorylation sites in IRS-1 was shown in vitro by a 75-80% decrease in the incorporation of phosphate into an IRS-1 triple mutant in which Ser-307, Ser-323 and Ser-574 were replaced by Ala. More importantly, the mutation of these three sites completely abrogated the inhibitory effect of PKCdelta on IRS-1 tyrosine phosphorylation in vitro. Tyrosine 349-357 insulin receptor substrate 1 Homo sapiens 153-158 14583092-7 2004 The importance of three of the PKCdelta phosphorylation sites in IRS-1 was shown in vitro by a 75-80% decrease in the incorporation of phosphate into an IRS-1 triple mutant in which Ser-307, Ser-323 and Ser-574 were replaced by Ala. More importantly, the mutation of these three sites completely abrogated the inhibitory effect of PKCdelta on IRS-1 tyrosine phosphorylation in vitro. Tyrosine 349-357 insulin receptor substrate 1 Homo sapiens 153-158 14583092-8 2004 These results indicate that PKCdelta modulates the ability of the insulin receptor to tyrosine-phosphorylate IRS-1 by direct phosphorylation of the IRS-1 molecule. Tyrosine 86-94 insulin receptor substrate 1 Homo sapiens 109-114 14583092-8 2004 These results indicate that PKCdelta modulates the ability of the insulin receptor to tyrosine-phosphorylate IRS-1 by direct phosphorylation of the IRS-1 molecule. Tyrosine 86-94 insulin receptor substrate 1 Homo sapiens 148-153 15122091-3 2004 Tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) and its binding to phosphatidylinositol 3-kinase (PI 3-kinase) are critical events in the insulin signalling cascade leading to insulin-stimulated glucose transport. Tyrosine 0-8 insulin receptor substrate 1 Homo sapiens 28-56 15122091-3 2004 Tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) and its binding to phosphatidylinositol 3-kinase (PI 3-kinase) are critical events in the insulin signalling cascade leading to insulin-stimulated glucose transport. Tyrosine 0-8 insulin receptor substrate 1 Homo sapiens 58-63 15122091-4 2004 Modification of IRS-1 by serine phosphorylation could be one of the mechanisms leading to a decrease in IRS-1 tyrosine phosphorylation, PI 3-kinase activity and glucose transport. Tyrosine 110-118 insulin receptor substrate 1 Homo sapiens 16-21 15122091-4 2004 Modification of IRS-1 by serine phosphorylation could be one of the mechanisms leading to a decrease in IRS-1 tyrosine phosphorylation, PI 3-kinase activity and glucose transport. Tyrosine 110-118 insulin receptor substrate 1 Homo sapiens 104-109 14668342-5 2004 EN transformation is associated with constitutive tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1). Tyrosine 50-58 insulin receptor substrate 1 Homo sapiens 108-113 14516276-8 2003 We speculate that if PTPL1 was recruited to the plasma membrane by increasing levels of PtdIns(3,4) P (2), it could trigger a negative feedback loop in which phosphoinositide-3-kinase-dependent or other signalling pathways could be switched off by the phosphatase-catalysed dephosphorylation of receptor tyrosine kinases or tyrosine phosphorylated adaptor proteins such as IRS1 or IRS2. Tyrosine 304-312 insulin receptor substrate 1 Homo sapiens 373-377 14602724-7 2004 Indeed, insulin induces the following: (i) tyrosine phosphorylation of the insulin receptor, the insulin receptor substrate-1 (IRS-1) and G(i)alpha(2); (ii) co-precipitation of IRS-1 with G(i)alpha(2) but not with other G alpha subunits. Tyrosine 43-51 insulin receptor substrate 1 Homo sapiens 127-132 14693696-4 2004 In 3T3-L1 adipocytes, DHEA increases tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and IRS-2 and stimulates IRS-1- and IRS-2-associated phosphatidylinositol (PI) 3-kinase activity with no effects on either insulin receptor or Akt phosphorylation. Tyrosine 37-45 insulin receptor substrate 1 Homo sapiens 65-99 14559999-5 2003 The binding occurs within the cytoplasm, engages the N-terminal domain of IRS-1, and is attenuated by IGF-I-mediated IRS-1 tyrosine phosphorylation. Tyrosine 123-131 insulin receptor substrate 1 Homo sapiens 74-79 14559999-5 2003 The binding occurs within the cytoplasm, engages the N-terminal domain of IRS-1, and is attenuated by IGF-I-mediated IRS-1 tyrosine phosphorylation. Tyrosine 123-131 insulin receptor substrate 1 Homo sapiens 117-122 14641015-3 2003 Tyrosine phosphorylation of IRS-1 (insulin receptor substrate 1) and its binding to PI 3-kinase (phosphoinositide 3-kinase) are critical events in the insulin signalling cascade leading to insulin-stimulated glucose transport. Tyrosine 0-8 insulin receptor substrate 1 Homo sapiens 28-33 14641015-3 2003 Tyrosine phosphorylation of IRS-1 (insulin receptor substrate 1) and its binding to PI 3-kinase (phosphoinositide 3-kinase) are critical events in the insulin signalling cascade leading to insulin-stimulated glucose transport. Tyrosine 0-8 insulin receptor substrate 1 Homo sapiens 35-63 14641015-6 2003 Modification of IRS-1 by serine phosphorylation could be one of the mechanisms leading to a decrease in IRS-1 tyrosine phosphorylation, PI 3-kinase activity and glucose transport. Tyrosine 110-118 insulin receptor substrate 1 Homo sapiens 16-21 14641015-6 2003 Modification of IRS-1 by serine phosphorylation could be one of the mechanisms leading to a decrease in IRS-1 tyrosine phosphorylation, PI 3-kinase activity and glucose transport. Tyrosine 110-118 insulin receptor substrate 1 Homo sapiens 104-109 14641043-3 2003 Down-regulation of insulin receptor tyrosine phosphorylation and subsequent steps in the insulin signalling pathway, including insulin receptor substrate-1 (IRS-1)-associated phosphoinositide 3-kinase (PI3K), Akt kinase serine phosphorylation and activity and glucose transporter (GLUT-4) protein content, are evident in skeletal muscle after eccentric exercise. Tyrosine 36-44 insulin receptor substrate 1 Homo sapiens 127-155 14641043-3 2003 Down-regulation of insulin receptor tyrosine phosphorylation and subsequent steps in the insulin signalling pathway, including insulin receptor substrate-1 (IRS-1)-associated phosphoinositide 3-kinase (PI3K), Akt kinase serine phosphorylation and activity and glucose transporter (GLUT-4) protein content, are evident in skeletal muscle after eccentric exercise. Tyrosine 36-44 insulin receptor substrate 1 Homo sapiens 157-162 14647049-7 2003 In contrast, insulin-stimulated IRS-1 tyrosine phosphorylation was decreased by 2-fold in HCV-infected subjects compared with non-HCV-infected subjects (P <.05). Tyrosine 38-46 insulin receptor substrate 1 Homo sapiens 32-37 14647049-8 2003 The observed reductions in IRS-1 tyrosine phosphorylation were accompanied by a 3.4-fold decrease in IRS-1/p85 phosphatidylinositol 3-kinase (PI3-kinase) association and a 2.5-fold decrease in IRS-1-associated PI3-kinase enzymatic activity (P <.05 vs. non-HCV). Tyrosine 33-41 insulin receptor substrate 1 Homo sapiens 27-32 14647049-8 2003 The observed reductions in IRS-1 tyrosine phosphorylation were accompanied by a 3.4-fold decrease in IRS-1/p85 phosphatidylinositol 3-kinase (PI3-kinase) association and a 2.5-fold decrease in IRS-1-associated PI3-kinase enzymatic activity (P <.05 vs. non-HCV). Tyrosine 33-41 insulin receptor substrate 1 Homo sapiens 101-106 14647049-8 2003 The observed reductions in IRS-1 tyrosine phosphorylation were accompanied by a 3.4-fold decrease in IRS-1/p85 phosphatidylinositol 3-kinase (PI3-kinase) association and a 2.5-fold decrease in IRS-1-associated PI3-kinase enzymatic activity (P <.05 vs. non-HCV). Tyrosine 33-41 insulin receptor substrate 1 Homo sapiens 101-106 14647049-13 2003 insulin signaling defects in hepatic IRS-1 tyrosine phosphorylation and PI3-kinase association/activation may contribute to insulin resistance, which leads to the development of type 2 diabetes mellitus in patients with HCV infection. Tyrosine 43-51 insulin receptor substrate 1 Homo sapiens 37-42 12960057-10 2003 Pretreatment of cells with EGF, FGF, or PDGF for 24 h reduced IGF-I-induced tyrosine phosphorylation per molecule of IRS-1. Tyrosine 76-84 insulin receptor substrate 1 Homo sapiens 117-122 12960057-13 2003 They further suggest that the FGF-induced increase in IRS-1 counterbalances the inhibition of IRS-1 tyrosine phosphorylation to allow normal stimulation of IGF-I-induced PI 3-kinase activity. Tyrosine 100-108 insulin receptor substrate 1 Homo sapiens 54-59 12960057-13 2003 They further suggest that the FGF-induced increase in IRS-1 counterbalances the inhibition of IRS-1 tyrosine phosphorylation to allow normal stimulation of IGF-I-induced PI 3-kinase activity. Tyrosine 100-108 insulin receptor substrate 1 Homo sapiens 94-99 12882909-6 2003 RSG therapy had no effect on basal or insulin-stimulated insulin receptor tyrosine phosphorylation but increased insulin stimulation of IRS-1 tyrosine phosphorylation (1.13 +/- 0.11 to 1.56 +/- 0.17 density units; P < 0.01 vs. prerosiglitazone) and p85 association with IRS-1 (1.00 +/- 0.06 to 1.27 +/- 0.07 activity units; P < 0.05 vs. prerosiglitazone). Tyrosine 142-150 insulin receptor substrate 1 Homo sapiens 136-141 12866995-6 2003 This results in reduction of tyrosine phosphorylation of the insulin receptor substrate-1 and inhibits activation of phosphoinositol-3 kinase, an enzyme that is essential for normal insulin-stimulated glucose uptake. Tyrosine 29-37 insulin receptor substrate 1 Homo sapiens 61-89 12882909-7 2003 In control and type 2 diabetic subjects, TGD/nonoxidative glucose disposal correlated positively with the insulin-stimulated increments in IRS-1 tyrosine phosphorylation (r = 0.52/r = 0.57, P < 0.01) and inversely with the plasma FFA concentration during the insulin clamp (r = -0.55/r = -0.53, P < 0.01). Tyrosine 145-153 insulin receptor substrate 1 Homo sapiens 139-144 12767053-8 2003 The acute actions of ACE inhibitors on skeletal muscle glucose transport are associated with upregulation of insulin signaling, including enhanced IRS-1 tyrosine phosphorylation and phosphatidylinositol-3-kinase activity, and ultimately with increased cell-surface GLUT-4 glucose transporter protein. Tyrosine 153-161 insulin receptor substrate 1 Homo sapiens 147-152 12730242-2 2003 We show here that, despite normal activation of insulin receptor, hyperosmotic stress inhibits both tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and IRS-1-associated phosphoinositide 3 (PI 3)-kinase activity in response to physiological insulin concentrations. Tyrosine 100-108 insulin receptor substrate 1 Homo sapiens 128-156 12730242-2 2003 We show here that, despite normal activation of insulin receptor, hyperosmotic stress inhibits both tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and IRS-1-associated phosphoinositide 3 (PI 3)-kinase activity in response to physiological insulin concentrations. Tyrosine 100-108 insulin receptor substrate 1 Homo sapiens 158-163 12730242-6 2003 The inhibition of mTOR completely reversed the inhibitory effect of hyperosmotic stress on insulin-induced IRS-1 tyrosine phosphorylation and PI 3-kinase activation. Tyrosine 113-121 insulin receptor substrate 1 Homo sapiens 107-112 14584587-7 2003 This controls many aspects of IRS-1, including its interaction with the insulin receptor and subsequent tyrosine phosphorylation, as well as its subcellular distribution and targeting for degradation by the proteasome. Tyrosine 104-112 insulin receptor substrate 1 Homo sapiens 30-35 12765939-4 2003 Investigating the causes of the reduced tyrosine phosphorylation of IRS-1, we found a more than twofold increase in the basal phosphorylation of IRS-1 on serine 636 in myotubes from patients with diabetes. Tyrosine 40-48 insulin receptor substrate 1 Homo sapiens 68-73 12765939-4 2003 Investigating the causes of the reduced tyrosine phosphorylation of IRS-1, we found a more than twofold increase in the basal phosphorylation of IRS-1 on serine 636 in myotubes from patients with diabetes. Tyrosine 40-48 insulin receptor substrate 1 Homo sapiens 145-150 12765939-6 2003 These results suggest that IRS-1 phosphorylation on serine 636 might be involved in the reduced phosphorylation of IRS-1 on tyrosine and in the subsequent alteration of insulin-induced PI 3-kinase activation. Tyrosine 124-132 insulin receptor substrate 1 Homo sapiens 27-32 12765939-6 2003 These results suggest that IRS-1 phosphorylation on serine 636 might be involved in the reduced phosphorylation of IRS-1 on tyrosine and in the subsequent alteration of insulin-induced PI 3-kinase activation. Tyrosine 124-132 insulin receptor substrate 1 Homo sapiens 115-120 12755958-4 2003 Interestingly, this single tyrosine residue represents a binding site for several signalling molecules including SHC, Enigma, SNT/FRS2, DOK and IRS1 and is responsible for activation of the RAS/ERK, PI3-K/AKT, JNK, p38MAPK and ERK5 signalling pathways. Tyrosine 27-35 insulin receptor substrate 1 Homo sapiens 144-148 12800089-2 2003 Here we show that simultaneous inhibition of IRS-1 tyrosine dephosphorylation and proteasomal degradation synergistically augments insulin-responsive glucose uptake. Tyrosine 51-59 insulin receptor substrate 1 Homo sapiens 45-50 12525499-11 2003 Finally, reconstitution of IRS-1(-/-) brown adipocytes with the IRS-1 mutants IRS-1(Phe-895), which lacks IRS-1/growth factor receptor binding protein 2 binding but not IRS-1/p85-PI 3-kinase binding, or with IRS-1(Tyr-608/Tyr-628/Tyr-658), which only binds p85-PI 3-kinase, induced UCP-1 expression and transactivated the UCP-1 promoter. Tyrosine 214-217 insulin receptor substrate 1 Homo sapiens 64-69 12560330-11 2003 This was associated with inhibition of hepatic insulin-dependent receptor autophosphorylation and IRS-1 tyrosine phosphorylation. Tyrosine 104-112 insulin receptor substrate 1 Homo sapiens 98-103 12740426-6 2003 Physiological hyperinsulinaemia increased tyrosine phosphorylation of insulin receptor substrate (IRS)-1 by approximately 2.5-fold, IRS-1-associated phosphatidylinositol 3-kinase (PI-3-kinase) activity by approximately 2-fold and Akt (protein kinase B) phosphorylation by approximately 3-fold, with similar responses between healthy subjects and CHF patients. Tyrosine 42-50 insulin receptor substrate 1 Homo sapiens 70-104 12639902-7 2003 In human skeletal muscle cells, both IRS-1 and IRS-2 are rapidly phosphorylated on tyrosine in response to insulin, whereas essentially no tyrosine phosphorylation of IRS-4 was observed in response to both insulin and IGF-I. Tyrosine 83-91 insulin receptor substrate 1 Homo sapiens 37-42 12525499-11 2003 Finally, reconstitution of IRS-1(-/-) brown adipocytes with the IRS-1 mutants IRS-1(Phe-895), which lacks IRS-1/growth factor receptor binding protein 2 binding but not IRS-1/p85-PI 3-kinase binding, or with IRS-1(Tyr-608/Tyr-628/Tyr-658), which only binds p85-PI 3-kinase, induced UCP-1 expression and transactivated the UCP-1 promoter. Tyrosine 214-217 insulin receptor substrate 1 Homo sapiens 64-69 12525499-11 2003 Finally, reconstitution of IRS-1(-/-) brown adipocytes with the IRS-1 mutants IRS-1(Phe-895), which lacks IRS-1/growth factor receptor binding protein 2 binding but not IRS-1/p85-PI 3-kinase binding, or with IRS-1(Tyr-608/Tyr-628/Tyr-658), which only binds p85-PI 3-kinase, induced UCP-1 expression and transactivated the UCP-1 promoter. Tyrosine 214-217 insulin receptor substrate 1 Homo sapiens 64-69 12525499-11 2003 Finally, reconstitution of IRS-1(-/-) brown adipocytes with the IRS-1 mutants IRS-1(Phe-895), which lacks IRS-1/growth factor receptor binding protein 2 binding but not IRS-1/p85-PI 3-kinase binding, or with IRS-1(Tyr-608/Tyr-628/Tyr-658), which only binds p85-PI 3-kinase, induced UCP-1 expression and transactivated the UCP-1 promoter. Tyrosine 214-217 insulin receptor substrate 1 Homo sapiens 64-69 12525499-11 2003 Finally, reconstitution of IRS-1(-/-) brown adipocytes with the IRS-1 mutants IRS-1(Phe-895), which lacks IRS-1/growth factor receptor binding protein 2 binding but not IRS-1/p85-PI 3-kinase binding, or with IRS-1(Tyr-608/Tyr-628/Tyr-658), which only binds p85-PI 3-kinase, induced UCP-1 expression and transactivated the UCP-1 promoter. Tyrosine 214-217 insulin receptor substrate 1 Homo sapiens 64-69 12510059-2 2003 One potential mechanism for this is that Ser/Thr phosphorylation decreases the ability of IRS-1 to be tyrosine-phosphorylated by the insulin receptor. Tyrosine 102-110 insulin receptor substrate 1 Homo sapiens 90-95 12577306-3 2003 Tyrosine phosphorylation of insulin receptor substrate 1 is detected when enriched by immunoprecipitation with anti-PI3K antibody. Tyrosine 0-8 insulin receptor substrate 1 Homo sapiens 28-56 12554784-5 2003 Finally, the MKK7 mutant, which activates JNK, reduced tyrosine phosphorylation of IRS-1 and IRS-2 and IRS-associated PI3K activity without affecting expression of the IR, IRS-1, or IRS-2. Tyrosine 55-63 insulin receptor substrate 1 Homo sapiens 83-88 12554784-3 2003 The MEK1 mutant, which activates ERK, markedly down-regulated expression of the insulin receptor (IR) and its major substrates, IRS-1 and IRS-2, mRNA and protein, and in turn reduced tyrosine phosphorylation of IR as well as IRS-1 and IRS-2 and their associated phosphatidyl inositol 3-kinase (PI3K) activity. Tyrosine 183-191 insulin receptor substrate 1 Homo sapiens 128-133 12554784-3 2003 The MEK1 mutant, which activates ERK, markedly down-regulated expression of the insulin receptor (IR) and its major substrates, IRS-1 and IRS-2, mRNA and protein, and in turn reduced tyrosine phosphorylation of IR as well as IRS-1 and IRS-2 and their associated phosphatidyl inositol 3-kinase (PI3K) activity. Tyrosine 183-191 insulin receptor substrate 1 Homo sapiens 225-230 12540590-4 2003 Here, we report that insulin induces tyrosine phosphorylation of the insulin receptor and IRS-1 and -2, increases binding of activated IRS-1 and -2 to the regulatory subunit of PI3K, and activates protein kinase B/Akt, a downstream target of PI3K. Tyrosine 37-45 insulin receptor substrate 1 Homo sapiens 90-102 12511230-5 2003 Tyrosine phosphorylation of IR?, IRS1, and IRS2 was increased by 2.7 fold (P < 0.01), 6.8 fold (P < 0.01), and 2.3 fold (P <0.01) of chronically insulin-treated cells alone, respectively, after metformin 0.1 mmol/L was added. Tyrosine 0-8 insulin receptor substrate 1 Homo sapiens 33-37 12518028-7 2003 During differentiation with ritonavir (i.e., 1-11 days post addition of differentiating cocktail), insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation was ascertained (day 11) and found to be decreased in the ritonavir exposed cells when compared with control cells. Tyrosine 136-144 insulin receptor substrate 1 Homo sapiens 99-127 12518028-7 2003 During differentiation with ritonavir (i.e., 1-11 days post addition of differentiating cocktail), insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation was ascertained (day 11) and found to be decreased in the ritonavir exposed cells when compared with control cells. Tyrosine 136-144 insulin receptor substrate 1 Homo sapiens 129-134 12518028-9 2003 These effects may be subsequent to decreased insulin binding and/or IRS-1 tyrosine phosphorylation. Tyrosine 74-82 insulin receptor substrate 1 Homo sapiens 68-73 12220227-2 2002 Here we show that stimulation by insulin of freshly isolated primary adipocytes resulted in the expected rapid tyrosine phosphorylation of the insulin receptor, IRS-1 and IRS-3. Tyrosine 111-119 insulin receptor substrate 1 Homo sapiens 161-166 12220227-3 2002 Inhibition of PI 3-kinase enhanced the insulin-stimulated phosphorylation of IRS-1 on (i) Tyr(612) and Tyr(941) (p85 binding sites), concomitant with an increased association of the p85 subunit of PI 3-kinase; (ii) Tyr(896) (a Grb2 binding site); and (iii) Tyr(1229) (an SHP-2 binding site), although little or no binding of SHP-2 to IRS-1 was detectable under any conditions. Tyrosine 90-93 insulin receptor substrate 1 Homo sapiens 77-82 12220227-3 2002 Inhibition of PI 3-kinase enhanced the insulin-stimulated phosphorylation of IRS-1 on (i) Tyr(612) and Tyr(941) (p85 binding sites), concomitant with an increased association of the p85 subunit of PI 3-kinase; (ii) Tyr(896) (a Grb2 binding site); and (iii) Tyr(1229) (an SHP-2 binding site), although little or no binding of SHP-2 to IRS-1 was detectable under any conditions. Tyrosine 103-106 insulin receptor substrate 1 Homo sapiens 77-82 12220227-3 2002 Inhibition of PI 3-kinase enhanced the insulin-stimulated phosphorylation of IRS-1 on (i) Tyr(612) and Tyr(941) (p85 binding sites), concomitant with an increased association of the p85 subunit of PI 3-kinase; (ii) Tyr(896) (a Grb2 binding site); and (iii) Tyr(1229) (an SHP-2 binding site), although little or no binding of SHP-2 to IRS-1 was detectable under any conditions. Tyrosine 103-106 insulin receptor substrate 1 Homo sapiens 77-82 12220227-3 2002 Inhibition of PI 3-kinase enhanced the insulin-stimulated phosphorylation of IRS-1 on (i) Tyr(612) and Tyr(941) (p85 binding sites), concomitant with an increased association of the p85 subunit of PI 3-kinase; (ii) Tyr(896) (a Grb2 binding site); and (iii) Tyr(1229) (an SHP-2 binding site), although little or no binding of SHP-2 to IRS-1 was detectable under any conditions. Tyrosine 103-106 insulin receptor substrate 1 Homo sapiens 77-82 12453891-6 2002 The IL-6 effect is characterized by a decreased tyrosine phosphorylation of IR substrate (IRS)-1 and decreased association of the p85 subunit of phosphatidylinositol 3-kinase with IRS-1 in response to physiologic insulin levels. Tyrosine 48-56 insulin receptor substrate 1 Homo sapiens 76-96 12413892-4 2002 Here we report that SP-A treatment leads to rapid tyrosine-specific phosphorylation of several important proteins in lung epithelial cells including insulin receptor substrate-1 (IRS-1), an upstream activator of PI3K. Tyrosine 50-58 insulin receptor substrate 1 Homo sapiens 149-177 12413892-4 2002 Here we report that SP-A treatment leads to rapid tyrosine-specific phosphorylation of several important proteins in lung epithelial cells including insulin receptor substrate-1 (IRS-1), an upstream activator of PI3K. Tyrosine 50-58 insulin receptor substrate 1 Homo sapiens 179-184 12237252-5 2002 3 Chronic insulin treatment resulted in 60 and 40% reduction in insulin-stimulated tyrosine phosphorylation of IR and IRS-1, respectively. Tyrosine 83-91 insulin receptor substrate 1 Homo sapiens 118-123 12237252-6 2002 Treatment with metformin was able to increase the tyrosine phosphorylation of IR and IRS-1 by 100 and 90% respectively. Tyrosine 50-58 insulin receptor substrate 1 Homo sapiens 85-90 12237252-4 2002 Insulin-stimulated tyrosine phosphorylation of insulin receptor (IR) and insulin receptor substrate-1 (IRS-1) was determined. Tyrosine 19-27 insulin receptor substrate 1 Homo sapiens 103-108 12242307-1 2002 Receptor-mediated tyrosine phosphorylation of the insulin receptor substrate 1 (IRS-1) is required for the propagation of many of insulin"s biological effects. Tyrosine 18-26 insulin receptor substrate 1 Homo sapiens 50-78 12242307-1 2002 Receptor-mediated tyrosine phosphorylation of the insulin receptor substrate 1 (IRS-1) is required for the propagation of many of insulin"s biological effects. Tyrosine 18-26 insulin receptor substrate 1 Homo sapiens 80-85 12207909-0 2002 Proteasome inhibitors regulate tyrosine phosphorylation of IRS-1 and insulin signaling in adipocytes. Tyrosine 31-39 insulin receptor substrate 1 Homo sapiens 59-64 12207909-3 2002 We report here that the insulin-induced IRS-1 tyrosine phosphorylation and PI 3-kinase association to IRS-1 were strongly sustained by the proteasome inhibitors, MG132 and lactacystin. Tyrosine 46-54 insulin receptor substrate 1 Homo sapiens 40-45 12207909-3 2002 We report here that the insulin-induced IRS-1 tyrosine phosphorylation and PI 3-kinase association to IRS-1 were strongly sustained by the proteasome inhibitors, MG132 and lactacystin. Tyrosine 46-54 insulin receptor substrate 1 Homo sapiens 102-107 12172480-10 2002 TNF-alpha results in insulin insensitivity, indirectly by stimulating stress hormone production and directly by sustained induction of SOCS-3 which decreases insulin-induced insulin receptor substrate 1 (IRS1) tyrosine phosphorylation and its association with the p85, regulatory subunit of phosphatidylinositol-3 kinase; and by negative regulation of PPAR gamma. Tyrosine 210-218 insulin receptor substrate 1 Homo sapiens 204-208 11877394-4 2002 The IRS-1 domain responsible for a direct JC virus T-antigen binding was localized within the N-terminal portion of IRS-1 molecule, and the binding was independent from IRS-1 tyrosine phosphorylation and was strongly inhibited by IRS-1 serine phosphorylation. Tyrosine 175-183 insulin receptor substrate 1 Homo sapiens 4-9 12207909-8 2002 In conclusion, proteasome inhibitors can regulate the tyrosine phosphorylation of IRS-1 and the downstream insulin signaling pathway, leading to glucose transport. Tyrosine 54-62 insulin receptor substrate 1 Homo sapiens 82-87 12145147-4 2002 Insulin-induced tyrosine phosphorylation of insulin receptor substrate (IRS)-1 was completely blocked, with unaltered expression of IRS-1. Tyrosine 16-24 insulin receptor substrate 1 Homo sapiens 44-78 12107372-4 2002 Other possible mechanisms of insulin resistance in cytokine-treated cells include nitration of insulin receptor substrate-1 tyrosine residues by nitric oxide-derived reactive nitrogen species as well as direct interference with insulin signaling molecules further downstream such as protein kinase B/Akt. Tyrosine 124-132 insulin receptor substrate 1 Homo sapiens 95-123 12033942-5 2002 Dephosphorylation of basal Ser/Thr sites on F-IRS-1 also significantly reduced tyrosine phosphorylation by the IGF-1 receptor. Tyrosine 79-87 insulin receptor substrate 1 Homo sapiens 46-51 12033942-9 2002 Dephosphorylation of IRS-1 and IRS-2 immunoprecipitated from serum-deprived cells, however, resulted in inhibition of tyrosine phosphorylation by the insulin receptor. Tyrosine 118-126 insulin receptor substrate 1 Homo sapiens 21-26 12033942-10 2002 These data suggest that Ser/Thr phosphorylation can have both a positive and a negative regulatory role on tyrosine phosphorylation of IRS-1 and IRS-2 by insulin and IGF-1 receptors. Tyrosine 107-115 insulin receptor substrate 1 Homo sapiens 135-140 11983706-4 2002 HG culturing also enhanced insulin-stimulated insulin receptor and insulin receptor substrate 1 (IRS1) tyrosine phosphorylations while decreasing basal phosphorylations. Tyrosine 103-111 insulin receptor substrate 1 Homo sapiens 97-101 11983706-9 2002 However, HG culturing largely redistributed SHP-2 to the internal membrane compartment, where tyrosine-phosphorylated IRS1 predominantly localizes. Tyrosine 94-102 insulin receptor substrate 1 Homo sapiens 118-122 12058282-3 2002 In this model, IGF-I did not activate the focal adhesion kinase, whereas it induced tyrosine phosphorylation of the insulin receptor substrate-1 and activation of the extracellular signal-related kinase 1 and 2, p38, phosphatidylinositol 3"-kinase and protein kinase B/Akt. Tyrosine 84-92 insulin receptor substrate 1 Homo sapiens 116-144 12033942-1 2002 Insulin receptor substrates (IRS) 1 and 2 are phosphorylated on serine/threonine (Ser/Thr) residues in quiescent cells (basal phosphorylation), and phosphorylation on both Ser/Thr and tyrosine residues is increased upon insulin stimulation. Tyrosine 184-192 insulin receptor substrate 1 Homo sapiens 0-41 12033942-3 2002 As expected, hyperphosphorylation of F-IRS-1 and F-IRS-2 by GSK3beta decreased their subsequent phosphorylation on tyrosine residues by the insulin receptor. Tyrosine 115-123 insulin receptor substrate 1 Homo sapiens 39-44 12033942-4 2002 Surprisingly, however, dephosphorylation of the basal Ser/Thr phosphorylation sites impaired subsequent phosphorylation on tyrosine, suggesting that basal Ser/Thr phosphorylation of F-IRS-1 and F-IRS-2 plays a positive role in phosphorylation by the insulin receptor tyrosine kinase. Tyrosine 123-131 insulin receptor substrate 1 Homo sapiens 184-189 11877394-4 2002 The IRS-1 domain responsible for a direct JC virus T-antigen binding was localized within the N-terminal portion of IRS-1 molecule, and the binding was independent from IRS-1 tyrosine phosphorylation and was strongly inhibited by IRS-1 serine phosphorylation. Tyrosine 175-183 insulin receptor substrate 1 Homo sapiens 116-121 11877394-4 2002 The IRS-1 domain responsible for a direct JC virus T-antigen binding was localized within the N-terminal portion of IRS-1 molecule, and the binding was independent from IRS-1 tyrosine phosphorylation and was strongly inhibited by IRS-1 serine phosphorylation. Tyrosine 175-183 insulin receptor substrate 1 Homo sapiens 116-121 11877394-4 2002 The IRS-1 domain responsible for a direct JC virus T-antigen binding was localized within the N-terminal portion of IRS-1 molecule, and the binding was independent from IRS-1 tyrosine phosphorylation and was strongly inhibited by IRS-1 serine phosphorylation. Tyrosine 175-183 insulin receptor substrate 1 Homo sapiens 116-121 11779863-2 2002 Similar to TNF, cycloheximide and anisomycin stimulated serine phosphorylation of IRS-1 and IRS-2, reduced their ability to interact with the insulin receptor, inhibited the insulin-induced tyrosine phosphorylation of IRS proteins, and diminished their association with phosphatidylinositol 3-kinase (PI3K). Tyrosine 190-198 insulin receptor substrate 1 Homo sapiens 82-87 11875115-1 2002 The appearance of a complex between tyrosine-phosphorylated insulin receptor substrate 1 (IRS-1) and PI3K in a high-speed pellet fraction (HSP) is thought to be a key event in insulin action. Tyrosine 36-44 insulin receptor substrate 1 Homo sapiens 90-95 11713219-6 2001 In this regard, IGF-1-induced tyrosine phosphorylation of IRS-1 was decreased by overexpressing both WT-Shc and 3F-Shc cells. Tyrosine 30-38 insulin receptor substrate 1 Homo sapiens 58-63 11788651-10 2002 Total tyrosine phosphorylated IRS-1 increased by 29% during the control clamps (P < 0.05), but by only 18% (NS) during the Intralipid studies. Tyrosine 6-14 insulin receptor substrate 1 Homo sapiens 30-35 11788651-17 2002 In summary, NEFA-induced insulin resistance is associated with an impairment of IRS-1 tyrosine phosphorylation and IRS-1-associated PI3K activation. Tyrosine 86-94 insulin receptor substrate 1 Homo sapiens 80-85 11723060-3 2001 In vivo insulin infusion increased skeletal muscle insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation (P = 0.01) and phosphatidylinositide 3-kinase (PI 3-kinase) activity (phosphotyrosine and IRS-1 associated) in control subjects (P < 0.02) but not in IGT relatives (NS). Tyrosine 88-96 insulin receptor substrate 1 Homo sapiens 81-86 11723060-4 2001 The incremental increase in insulin action on IRS-1 tyrosine phosphorylation was lower in IGT relatives versus control subjects (P < 0.05). Tyrosine 52-60 insulin receptor substrate 1 Homo sapiens 46-51 11786376-7 2002 During diestrus and proestrus when IGF-I levels were increasing, tyrosine phosphorylation of IRS-1 was increased up to 5.7-fold in the normal myometrium relative to estrus, when IGF-I levels were the lowest. Tyrosine 65-73 insulin receptor substrate 1 Homo sapiens 93-98 12674767-4 2002 Results showed that 1-min insulin stimulation rapidly induced tyrosine phosphorylation of IR beta and IRS-1, which in turn, resulting in association of PI 3-kinase with IRS-1. Tyrosine 62-70 insulin receptor substrate 1 Homo sapiens 102-107 12674767-4 2002 Results showed that 1-min insulin stimulation rapidly induced tyrosine phosphorylation of IR beta and IRS-1, which in turn, resulting in association of PI 3-kinase with IRS-1. Tyrosine 62-70 insulin receptor substrate 1 Homo sapiens 169-174 18521338-5 2002 However, upon insulin stimulation both IRS- 1 and IRS-2 were tyrosine phosphorylated with a similar kinetic in the respective cell lines; furthermore, after 1 min of insulin stimulation PI3-kinase associated with IRSs and after 2 min Shc was phosphorylated and associated with Grb2 with minor differences detectable among the various cell lines in the duration of phosphorylation and/or in their association irrespective of whether IRS-1 or IRS-2 were expressed. Tyrosine 61-69 insulin receptor substrate 1 Homo sapiens 39-45 11526109-11 2001 This raises the possibility that IRS-1 tyrosine phosphorylation may occur prior to plasma membrane translocation. Tyrosine 39-47 insulin receptor substrate 1 Homo sapiens 33-38 11682617-4 2001 Recent advances indicate that serine kinases may phosphorylate and thus inhibit the tyrosine phosphorylation of insulin receptor substrate-1, revealing an integration point of TNFalpha and insulin signaling pathways. Tyrosine 84-92 insulin receptor substrate 1 Homo sapiens 112-140 11679436-7 2001 In contrast, the FH(+) group had decreased insulin stimulation of insulin receptor substrate (IRS)-1 tyrosine phosphorylation (0.522 +/- 0.077 vs. 1.328 +/- 0.115 density units; P < 0.01) and association of PI 3-kinase activity with IRS-1 (0.299 +/- 0.053 vs. 0.466 +/- 0.098 activity units; P < 0.05). Tyrosine 101-109 insulin receptor substrate 1 Homo sapiens 66-100 11416032-6 2001 We found that ATA and EB mimicked the IGF-I effect on tyrosine phosphorylation of the IGF-I receptor (IGF-IR) and its major substrates, insulin receptor substrate-1 (IRS-1) and IRS-2; induced the association of these substrates with phosphatidylinositol 3-kinase and Grb2; and activated Akt kinase and p42/p44 mitogen-activated protein kinases. Tyrosine 54-62 insulin receptor substrate 1 Homo sapiens 136-164 11488908-3 2001 268, 25-34], epidermal growth factor (EGF) gave rise to transient tyrosine phosphorylation of insulin receptor substrates (IRS-1 and IRS-2), thereby activating the bound phosphatidylinositol 3-kinase in human epidermoid carcinoma A431 cells normally abundant in EGF receptors (EGFR) and Chinese hamster ovary (CHO) cells transfected with full-length EGFR. Tyrosine 66-74 insulin receptor substrate 1 Homo sapiens 123-128 11488908-7 2001 We suggest that tyrosine phosphorylation of IRS-1 or IRS-2 could mediate EGFR-induced activation of phosphatidylinositol 3-kinase in mammalian cells. Tyrosine 16-24 insulin receptor substrate 1 Homo sapiens 44-49 11438664-6 2001 Ligation of the alpha6beta4 receptor promotes tyrosine phosphorylation of IRS-1 and IRS-2 and increases their association with PI3K, as determined by coimmunoprecipitation. Tyrosine 46-54 insulin receptor substrate 1 Homo sapiens 74-79 11416002-0 2001 Tyr(612) and Tyr(632) in human insulin receptor substrate-1 are important for full activation of insulin-stimulated phosphatidylinositol 3-kinase activity and translocation of GLUT4 in adipose cells. Tyrosine 0-3 insulin receptor substrate 1 Homo sapiens 31-59 11416002-0 2001 Tyr(612) and Tyr(632) in human insulin receptor substrate-1 are important for full activation of insulin-stimulated phosphatidylinositol 3-kinase activity and translocation of GLUT4 in adipose cells. Tyrosine 13-16 insulin receptor substrate 1 Homo sapiens 31-59 11403293-9 2001 High-throughput drug screening and quantitative analysis for a specific pathway in tyrosine phosphorylation of IRS-1 in insulin signaling are also made possible in this system. Tyrosine 83-91 insulin receptor substrate 1 Homo sapiens 111-116 11748924-6 2001 We have found that leptin receptor, IRS-1 and the RNA-binding protein Sam68 are tyrosine phosphorylated upon leptin challenge in a dose-dependent manner. Tyrosine 80-88 insulin receptor substrate 1 Homo sapiens 36-41 11748924-7 2001 Moreover, tyrosine phosphorylation of IRS-1 and Sam68 promotes their association with p85, the regulatory subunit of PI3K, and this association leads to the stimulation of PI3K activity. Tyrosine 10-18 insulin receptor substrate 1 Homo sapiens 38-43 11557037-4 2001 SPR measurements showed that the tyrosine phosphorylation of IGF-1R induced by its extracellular ligand insulin-like growth factor-1 caused the receptor to bind with IRS-1 10 times faster than the unactivated receptor. Tyrosine 33-41 insulin receptor substrate 1 Homo sapiens 166-171 12536716-2 2001 Results showed that adipocytes treated with different high glucose (10, 15 and 25 mmol.L-1) for 24 hours showed to impair the basal and insulin-induced increase in glucose uptake in a dose-dependent manner and decreased significantly IRS1 tyrosine phosphorylation. Tyrosine 239-247 insulin receptor substrate 1 Homo sapiens 234-238 11416002-4 2001 Adding back both Tyr(612) and Tyr(632) fully restored IRS-1-associated PI3K activity, whereas adding back either Tyr(612) or Tyr(632) alone was associated with intermediate PI3K activity. Tyrosine 17-20 insulin receptor substrate 1 Homo sapiens 54-59 11416002-4 2001 Adding back both Tyr(612) and Tyr(632) fully restored IRS-1-associated PI3K activity, whereas adding back either Tyr(612) or Tyr(632) alone was associated with intermediate PI3K activity. Tyrosine 30-33 insulin receptor substrate 1 Homo sapiens 54-59 11416002-4 2001 Adding back both Tyr(612) and Tyr(632) fully restored IRS-1-associated PI3K activity, whereas adding back either Tyr(612) or Tyr(632) alone was associated with intermediate PI3K activity. Tyrosine 30-33 insulin receptor substrate 1 Homo sapiens 54-59 11416002-4 2001 Adding back both Tyr(612) and Tyr(632) fully restored IRS-1-associated PI3K activity, whereas adding back either Tyr(612) or Tyr(632) alone was associated with intermediate PI3K activity. Tyrosine 30-33 insulin receptor substrate 1 Homo sapiens 54-59 11416002-8 2001 Thus, both Tyr(612) and Tyr(632) are important for IRS-1 to fully activate PI3K and mediate translocation of GLUT4 in response to insulin. Tyrosine 11-14 insulin receptor substrate 1 Homo sapiens 51-56 11416002-8 2001 Thus, both Tyr(612) and Tyr(632) are important for IRS-1 to fully activate PI3K and mediate translocation of GLUT4 in response to insulin. Tyrosine 24-27 insulin receptor substrate 1 Homo sapiens 51-56 11416032-6 2001 We found that ATA and EB mimicked the IGF-I effect on tyrosine phosphorylation of the IGF-I receptor (IGF-IR) and its major substrates, insulin receptor substrate-1 (IRS-1) and IRS-2; induced the association of these substrates with phosphatidylinositol 3-kinase and Grb2; and activated Akt kinase and p42/p44 mitogen-activated protein kinases. Tyrosine 54-62 insulin receptor substrate 1 Homo sapiens 166-171 11287630-4 2001 Tumor necrosis factor (TNF) inhibited insulin-promoted tyrosine phosphorylation of IRS-1 and activated the Akt/protein kinase B serine-threonine kinase, a downstream target for phosphatidylinositol 3-kinase (PI 3-kinase). Tyrosine 55-63 insulin receptor substrate 1 Homo sapiens 83-88 11376126-4 2001 Oestradiol induced expression of IRS-1 results in enhanced tyrosine phosphorylation of IRS-1 after IGF-1 stimulation, followed by enhanced mitogen activated protein kinase, phosphoinositide 3" kinase, and Akt activation. Tyrosine 59-67 insulin receptor substrate 1 Homo sapiens 33-38 11376126-4 2001 Oestradiol induced expression of IRS-1 results in enhanced tyrosine phosphorylation of IRS-1 after IGF-1 stimulation, followed by enhanced mitogen activated protein kinase, phosphoinositide 3" kinase, and Akt activation. Tyrosine 59-67 insulin receptor substrate 1 Homo sapiens 87-92 11287630-1 2001 Tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) by the insulin receptor permits this docking protein to interact with signaling proteins that promote insulin action. Tyrosine 0-8 insulin receptor substrate 1 Homo sapiens 28-56 11287630-1 2001 Tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) by the insulin receptor permits this docking protein to interact with signaling proteins that promote insulin action. Tyrosine 0-8 insulin receptor substrate 1 Homo sapiens 58-63 11287630-5 2001 The effect of TNF on insulin-promoted tyrosine phosphorylation of IRS-1 was blocked by inhibition of PI 3-kinase and the PTEN tumor suppressor, which dephosphorylates the lipids that mediate PI 3-kinase functions, whereas constitutively active Akt impaired insulin-promoted IRS-1 tyrosine phosphorylation. Tyrosine 38-46 insulin receptor substrate 1 Homo sapiens 66-71 11287630-2 2001 Serine phosphorylation uncouples IRS-1 from the insulin receptor, thereby inhibiting its tyrosine phosphorylation and insulin signaling. Tyrosine 89-97 insulin receptor substrate 1 Homo sapiens 33-38 11287630-5 2001 The effect of TNF on insulin-promoted tyrosine phosphorylation of IRS-1 was blocked by inhibition of PI 3-kinase and the PTEN tumor suppressor, which dephosphorylates the lipids that mediate PI 3-kinase functions, whereas constitutively active Akt impaired insulin-promoted IRS-1 tyrosine phosphorylation. Tyrosine 38-46 insulin receptor substrate 1 Homo sapiens 274-279 11287630-5 2001 The effect of TNF on insulin-promoted tyrosine phosphorylation of IRS-1 was blocked by inhibition of PI 3-kinase and the PTEN tumor suppressor, which dephosphorylates the lipids that mediate PI 3-kinase functions, whereas constitutively active Akt impaired insulin-promoted IRS-1 tyrosine phosphorylation. Tyrosine 280-288 insulin receptor substrate 1 Homo sapiens 66-71 11287630-6 2001 Conversely, TNF inhibition of IRS-1 tyrosine phosphorylation was blocked by kinase dead Akt. Tyrosine 36-44 insulin receptor substrate 1 Homo sapiens 30-35 11287630-7 2001 Inhibition of IRS-1 tyrosine phosphorylation by TNF was blocked by rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), a downstream target of Akt. Tyrosine 20-28 insulin receptor substrate 1 Homo sapiens 14-19 11145958-1 2001 The pleckstrin homology (PH) domain of the insulin receptor substrate-1 (IRS-1) plays a role in directing this molecule to the insulin receptor, thereby regulating its tyrosine phosphorylation. Tyrosine 168-176 insulin receptor substrate 1 Homo sapiens 43-71 11145958-1 2001 The pleckstrin homology (PH) domain of the insulin receptor substrate-1 (IRS-1) plays a role in directing this molecule to the insulin receptor, thereby regulating its tyrosine phosphorylation. Tyrosine 168-176 insulin receptor substrate 1 Homo sapiens 73-78 11145958-6 2001 These results indicate that the PH domain of IRS-1, in addition to directing this protein to the receptor for tyrosine phosphorylation, functions in the ability of this molecule to stimulate subsequent responses. Tyrosine 110-118 insulin receptor substrate 1 Homo sapiens 45-50 11145958-7 2001 Thus, compromising the function of the PH domain, e.g. in insulin-resistant states, could decrease both the ability of IRS-1 to be tyrosine phosphorylated by the insulin receptor and to link to subsequent downstream targets. Tyrosine 131-139 insulin receptor substrate 1 Homo sapiens 119-124 11471071-0 2001 IRS-1 tyrosine phosphorylation reflects insulin-induced metabolic and mitogenic responses in 3T3-L1 pre-adipocytes. Tyrosine 6-14 insulin receptor substrate 1 Homo sapiens 0-5 11171109-1 2001 Insulin receptor substrate-1 (IRS-1) is a multi-domain protein that mediates signal transduction from receptors for insulin and other growth factors to a variety of downstream molecules through both tyrosine-phosphorylation-dependent and -independent interactions. Tyrosine 199-207 insulin receptor substrate 1 Homo sapiens 0-28 11171109-1 2001 Insulin receptor substrate-1 (IRS-1) is a multi-domain protein that mediates signal transduction from receptors for insulin and other growth factors to a variety of downstream molecules through both tyrosine-phosphorylation-dependent and -independent interactions. Tyrosine 199-207 insulin receptor substrate 1 Homo sapiens 30-35 11171109-2 2001 While the tyrosine-phosphorylation-dependent interactions mediated by IRS-1 have been well characterized, the molecular basis underlying the tyrosine-phosphorylation-independent IRS-1 interactions is largely unknown. Tyrosine 10-18 insulin receptor substrate 1 Homo sapiens 70-75 11162588-0 2001 Frap-dependent serine phosphorylation of IRS-1 inhibits IRS-1 tyrosine phosphorylation. Tyrosine 62-70 insulin receptor substrate 1 Homo sapiens 41-46 11162588-0 2001 Frap-dependent serine phosphorylation of IRS-1 inhibits IRS-1 tyrosine phosphorylation. Tyrosine 62-70 insulin receptor substrate 1 Homo sapiens 56-61 11162588-1 2001 We have previously shown that interferon-alpha (IFN alpha)-dependent tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) is impaired by serine phosphorylation of IRS-1 due to the reduced ability of serine phosphorylated IRS-1 to serve as a substrate for Janus kinase 1 (JAK1). Tyrosine 69-77 insulin receptor substrate 1 Homo sapiens 97-125 11162588-1 2001 We have previously shown that interferon-alpha (IFN alpha)-dependent tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) is impaired by serine phosphorylation of IRS-1 due to the reduced ability of serine phosphorylated IRS-1 to serve as a substrate for Janus kinase 1 (JAK1). Tyrosine 69-77 insulin receptor substrate 1 Homo sapiens 127-132 11162588-1 2001 We have previously shown that interferon-alpha (IFN alpha)-dependent tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) is impaired by serine phosphorylation of IRS-1 due to the reduced ability of serine phosphorylated IRS-1 to serve as a substrate for Janus kinase 1 (JAK1). Tyrosine 69-77 insulin receptor substrate 1 Homo sapiens 175-180 11162588-1 2001 We have previously shown that interferon-alpha (IFN alpha)-dependent tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) is impaired by serine phosphorylation of IRS-1 due to the reduced ability of serine phosphorylated IRS-1 to serve as a substrate for Janus kinase 1 (JAK1). Tyrosine 69-77 insulin receptor substrate 1 Homo sapiens 175-180 11313948-4 2001 Here we show that the Insulin Receptor Substrate-1 (IRS-1) is tyrosine phosphorylated and associated with the p85 regulatory subunit of PI3-K in response to Ret activation. Tyrosine 62-70 insulin receptor substrate 1 Homo sapiens 22-50 11313948-4 2001 Here we show that the Insulin Receptor Substrate-1 (IRS-1) is tyrosine phosphorylated and associated with the p85 regulatory subunit of PI3-K in response to Ret activation. Tyrosine 62-70 insulin receptor substrate 1 Homo sapiens 52-57 11313948-6 2001 The association with the PTB domain of IRS-1 depends on the phosphorylation of tyrosine 1062 of Ret. Tyrosine 79-87 insulin receptor substrate 1 Homo sapiens 39-44 11147790-0 2001 Serine/threonine phosphorylation of IRS-1 triggers its degradation: possible regulation by tyrosine phosphorylation. Tyrosine 91-99 insulin receptor substrate 1 Homo sapiens 36-41 11147790-4 2001 Wortmannin and rapamycin blocked this mobility shift of IRS-1, maintained the insulin-induced tyrosine phosphorylation of IRS-1, and blocked its degradation. Tyrosine 94-102 insulin receptor substrate 1 Homo sapiens 56-61 11147790-4 2001 Wortmannin and rapamycin blocked this mobility shift of IRS-1, maintained the insulin-induced tyrosine phosphorylation of IRS-1, and blocked its degradation. Tyrosine 94-102 insulin receptor substrate 1 Homo sapiens 122-127 11147790-9 2001 Thus, regulation of serine/threonine versus tyrosine phosphorylation may modulate IRS-1 degradation, affecting insulin sensitivity. Tyrosine 44-52 insulin receptor substrate 1 Homo sapiens 82-87 11043572-2 2000 Previous studies have demonstrated that TNFalpha confers insulin resistance by promoting phosphorylation of serine residues on insulin receptor substrate 1 (IRS-1), thereby diminishing subsequent insulin-induced tyrosine phosphorylation of IRS-1. Tyrosine 212-220 insulin receptor substrate 1 Homo sapiens 157-162 11162588-4 2001 Importantly, only FRAP-dependent IRS-1(511-772) serine phosphorylation inhibited by 50% subsequent JAK1-dependent tyrosine phosphorylation of IRS-1. Tyrosine 114-122 insulin receptor substrate 1 Homo sapiens 33-38 11162588-4 2001 Importantly, only FRAP-dependent IRS-1(511-772) serine phosphorylation inhibited by 50% subsequent JAK1-dependent tyrosine phosphorylation of IRS-1. Tyrosine 114-122 insulin receptor substrate 1 Homo sapiens 142-147 11162588-6 2001 Taken together, these data indicate that FRAP, but not p70(s6k), is a likely physiologic IRS-1 serine kinase that negatively regulates JAK1-dependent IRS-1 tyrosine phosphorylation and suggests that FRAP may modulate IRS-dependent cytokine signaling. Tyrosine 156-164 insulin receptor substrate 1 Homo sapiens 150-155 11160134-2 2001 Recently, we discovered that recombinant NH2-terminal Jun kinase phosphorylates IRS-1 at Ser307, which inhibits insulin-stimulated tyrosine phosphorylation of IRS-1. Tyrosine 131-139 insulin receptor substrate 1 Homo sapiens 80-85 11160134-2 2001 Recently, we discovered that recombinant NH2-terminal Jun kinase phosphorylates IRS-1 at Ser307, which inhibits insulin-stimulated tyrosine phosphorylation of IRS-1. Tyrosine 131-139 insulin receptor substrate 1 Homo sapiens 159-164 11018022-6 2000 In contrast to full-length PHIP, overexpression of the PH-binding region of PHIP has a pronounced inhibitory effect on insulin-induced IRS-1 tyrosine phosphorylation levels. Tyrosine 141-149 insulin receptor substrate 1 Homo sapiens 135-140 11006284-6 2000 Insulin treatment of 3T3-L1 adipocytes stimulated association of Fer with complexes containing tyrosine phosphorylated IRS-1 and PI 3-kinase but did not stimulate tyrosine phosphorylation of Fer. Tyrosine 95-103 insulin receptor substrate 1 Homo sapiens 119-124 11016454-5 2000 Dexamethasone did not alter tyrosine phosphorylation of insulin receptors, and it significantly decreased protein expression and tyrosine phosphorylation of insulin receptor substrate (IRS)-1. Tyrosine 129-137 insulin receptor substrate 1 Homo sapiens 157-191 11043572-2 2000 Previous studies have demonstrated that TNFalpha confers insulin resistance by promoting phosphorylation of serine residues on insulin receptor substrate 1 (IRS-1), thereby diminishing subsequent insulin-induced tyrosine phosphorylation of IRS-1. Tyrosine 212-220 insulin receptor substrate 1 Homo sapiens 240-245 11043572-6 2000 We observe that TNFalpha requires 2.5-4 h to markedly reduce insulin-triggered tyrosine phosphorylation of IRS-1 in 3T3-L1 adipocytes. Tyrosine 79-87 insulin receptor substrate 1 Homo sapiens 107-112 10430617-6 1999 RIN-WT showed a marked increase in both glucose- and insulin-stimulated tyrosine phosphorylation of IRS-1 compared with control RIN cells. Tyrosine 72-80 insulin receptor substrate 1 Homo sapiens 100-105 10669726-3 2000 IGF-I (10 nM) stimulation of MCF-7 breast cancer cells caused a transient tyrosine phosphorylation of IRS-1 that was maximal at 15 min and decreased thereafter. Tyrosine 74-82 insulin receptor substrate 1 Homo sapiens 102-107 10669726-4 2000 The decrease in tyrosine phosphorylation of IRS-1 was paralleled by an apparent decrease in IRS-1 levels. Tyrosine 16-24 insulin receptor substrate 1 Homo sapiens 44-49 10669726-4 2000 The decrease in tyrosine phosphorylation of IRS-1 was paralleled by an apparent decrease in IRS-1 levels. Tyrosine 16-24 insulin receptor substrate 1 Homo sapiens 92-97 10669726-6 2000 Insulin (10 nM) caused tyrosine phosphorylation of IRS-1 but not degradation, whereas high concentrations of insulin (10 microM) resulted in degradation of IRS-1. Tyrosine 23-31 insulin receptor substrate 1 Homo sapiens 51-56 10660596-0 2000 Tyrosine dephosphorylation and deactivation of insulin receptor substrate-1 by protein-tyrosine phosphatase 1B. Tyrosine 0-8 insulin receptor substrate 1 Homo sapiens 47-75 10660596-8 2000 Further studies revealed that the adaptor protein GRB2 strongly promoted the formation of a stable protein complex between tyrosine-phosphorylated IRS-1 and catalytically inactive PTP1B, increasing their co-immunoprecipitation from an equimolar solution by 13.5 +/- 3.3-fold (n = 7; p < 0.01). Tyrosine 123-131 insulin receptor substrate 1 Homo sapiens 147-152 10660596-9 2000 Inclusion of GRB2 in a reaction mixture of IRS-1 and active PTP1B also increased the overall rate of IRS-1 tyrosine dephosphorylation by 2.7-3.9-fold (p < 0.01). Tyrosine 107-115 insulin receptor substrate 1 Homo sapiens 101-106 10698364-2 2000 Ethanol inhibits IGF-IR tyrosine autophosphorylation, which subsequently interferes with the activation of key downstream signaling mediators including insulin-receptor substrate-1, phosphatidylinositol 3-kinase, and mitogen-activated protein (MAP) kinase. Tyrosine 24-32 insulin receptor substrate 1 Homo sapiens 152-180 10868945-4 2000 In contrast, insulin-stimulated tyrosine phosphorylation of IRS-1 and anti-phosphotyrosine-associated PI 3-kinase activity were reduced 40-55% in type 2 diabetic subjects at high insulin concentrations (2.4 and 60 nmol/l, respectively). Tyrosine 32-40 insulin receptor substrate 1 Homo sapiens 60-65 10655627-7 2000 The present approach will thus become a general method for screening agonists for one specific pathway in tyrosine phosphorylation of IRS-1 in insulin signaling, which is regulated by specific protein-protein interaction between a phosphorylated tyrosine in IRS-1 and its corresponding SH2 domain-containing protein such as PI-3 kinase, Grb2-Sos, or SHP2. Tyrosine 106-114 insulin receptor substrate 1 Homo sapiens 134-139 10655627-7 2000 The present approach will thus become a general method for screening agonists for one specific pathway in tyrosine phosphorylation of IRS-1 in insulin signaling, which is regulated by specific protein-protein interaction between a phosphorylated tyrosine in IRS-1 and its corresponding SH2 domain-containing protein such as PI-3 kinase, Grb2-Sos, or SHP2. Tyrosine 106-114 insulin receptor substrate 1 Homo sapiens 258-263 10655627-7 2000 The present approach will thus become a general method for screening agonists for one specific pathway in tyrosine phosphorylation of IRS-1 in insulin signaling, which is regulated by specific protein-protein interaction between a phosphorylated tyrosine in IRS-1 and its corresponding SH2 domain-containing protein such as PI-3 kinase, Grb2-Sos, or SHP2. Tyrosine 246-254 insulin receptor substrate 1 Homo sapiens 134-139 10655627-7 2000 The present approach will thus become a general method for screening agonists for one specific pathway in tyrosine phosphorylation of IRS-1 in insulin signaling, which is regulated by specific protein-protein interaction between a phosphorylated tyrosine in IRS-1 and its corresponding SH2 domain-containing protein such as PI-3 kinase, Grb2-Sos, or SHP2. Tyrosine 246-254 insulin receptor substrate 1 Homo sapiens 258-263 10798222-6 2000 Lycopene treatment markedly reduced the IGF-I stimulation of tyrosine phosphorylation of insulin receptor substrate 1 and binding capacity of the AP-1 transcription complex. Tyrosine 61-69 insulin receptor substrate 1 Homo sapiens 89-117 10497255-6 1999 Accordingly, overexpression of IRS-1(4A), lacking the four potential PKB phosphorylation sites, markedly enhanced the rate of Tyr dephosphorylation of IRS-1, while inclusion of vanadate reversed this effect. Tyrosine 126-129 insulin receptor substrate 1 Homo sapiens 31-36 10497255-6 1999 Accordingly, overexpression of IRS-1(4A), lacking the four potential PKB phosphorylation sites, markedly enhanced the rate of Tyr dephosphorylation of IRS-1, while inclusion of vanadate reversed this effect. Tyrosine 126-129 insulin receptor substrate 1 Homo sapiens 151-156 10497255-8 1999 In contrast, insulin-stimulated PKB-mediated phosphorylation of Ser residues within the phosphotyrosine binding/SAIN domain of IRS-1 protects IRS-1 from the rapid action of protein-tyrosine phosphatases and enables it to maintain its Tyr-phosphorylated active conformation. Tyrosine 234-237 insulin receptor substrate 1 Homo sapiens 127-132 10497255-8 1999 In contrast, insulin-stimulated PKB-mediated phosphorylation of Ser residues within the phosphotyrosine binding/SAIN domain of IRS-1 protects IRS-1 from the rapid action of protein-tyrosine phosphatases and enables it to maintain its Tyr-phosphorylated active conformation. Tyrosine 234-237 insulin receptor substrate 1 Homo sapiens 142-147 10488146-2 1999 Here, we report that serine phosphorylation of IRS-1 induced by either okadaic acid (OA) or chronic insulin stimulation prevents interferon-alpha (IFN-alpha)-dependent IRS-1 tyrosine phosphorylation and IFN-alpha-dependent IRS-1/phosphatidylinositol 3"-kinase (PI3K) association. Tyrosine 174-182 insulin receptor substrate 1 Homo sapiens 47-52 10488146-2 1999 Here, we report that serine phosphorylation of IRS-1 induced by either okadaic acid (OA) or chronic insulin stimulation prevents interferon-alpha (IFN-alpha)-dependent IRS-1 tyrosine phosphorylation and IFN-alpha-dependent IRS-1/phosphatidylinositol 3"-kinase (PI3K) association. Tyrosine 174-182 insulin receptor substrate 1 Homo sapiens 168-173 10488146-4 1999 We found that treatment of U266 cells with OA induced serine phosphorylation of IRS-1 and completely blocked IFN-alpha-dependent tyrosine phosphorylation of IRS-1 and IFN-alpha-dependent IRS-1/PI3K association. Tyrosine 129-137 insulin receptor substrate 1 Homo sapiens 157-162 10488146-4 1999 We found that treatment of U266 cells with OA induced serine phosphorylation of IRS-1 and completely blocked IFN-alpha-dependent tyrosine phosphorylation of IRS-1 and IFN-alpha-dependent IRS-1/PI3K association. Tyrosine 129-137 insulin receptor substrate 1 Homo sapiens 157-162 10488146-6 1999 Chronic treatment of U266 cells with insulin led to a 50% reduction in IFN-alpha-dependent tyrosine phosphorylation of IRS-1 and IRS-1/PI3K association. Tyrosine 91-99 insulin receptor substrate 1 Homo sapiens 119-124 10488146-8 1999 Taken together, these data indicate that serine phosphorylation of IRS-1 prevents its subsequent tyrosine phosphorylation by JAK1 and suggest that IRS-1 serine phosphorylation may play a counter-regulatory role in pathways outside the insulin signaling system. Tyrosine 97-105 insulin receptor substrate 1 Homo sapiens 67-72 10500481-2 1999 Upon binding of insulin to cell-surface insulin receptor, the receptor phosphorylates tyrosine residues of insulin receptor substrate 1 (IRS-1) in the cell. Tyrosine 86-94 insulin receptor substrate 1 Homo sapiens 107-135 10500481-2 1999 Upon binding of insulin to cell-surface insulin receptor, the receptor phosphorylates tyrosine residues of insulin receptor substrate 1 (IRS-1) in the cell. Tyrosine 86-94 insulin receptor substrate 1 Homo sapiens 137-142 10500481-3 1999 A fluorescent indicator was designed by using synthetic phosphopeptide pY939 derived from the tyrosine phosphorylation domain of IRS-1 and its target protein SH2N containing an N-terminal SH2 domain of PI 3-kinase. Tyrosine 94-102 insulin receptor substrate 1 Homo sapiens 129-134 10480612-7 1999 Compared with nonpregnant control subjects, maximal insulin-stimulated IRS-1 tyrosine phosphorylation was significantly lower by 59 +/- 24% (mean +/- SD) (P < 0.05) and 62 +/- 28% (P < 0.05) in pregnant control and GDM subjects, respectively. Tyrosine 77-85 insulin receptor substrate 1 Homo sapiens 71-76 10480612-10 1999 These data indicate that insulin resistance to glucose transport during pregnancy is uniquely associated with a decrease in IRS-1 tyrosine phosphorylation, primarily due to decreased expression of IRS-1 protein. Tyrosine 130-138 insulin receptor substrate 1 Homo sapiens 124-129 10427145-5 1999 We report here that the vitamin D analogue EB1089 interferes with the IGF-IR signaling pathway by attenuating IGF-I-induced tyrosine phosphorylation of IRS-1, and to a lesser extent, IRS-2. Tyrosine 124-132 insulin receptor substrate 1 Homo sapiens 152-157 10427145-8 1999 Furthermore, we demonstrate that an antisense IGFBP-5 oligodeoxynucleotide attenuates EB1089-induced inhibition of IGF-I-stimulated tyrosine phosphorylation of IRS-1 and EB1089-induced IGFBP-5 accumulation. Tyrosine 132-140 insulin receptor substrate 1 Homo sapiens 160-165 10891367-11 2000 The relative phosphotyrosine (Tyr(P)) contents of the insulin receptor and its substrate 1 (IRS-1) were assessed in whole cell homogenates. Tyrosine 30-33 insulin receptor substrate 1 Homo sapiens 54-90 10866039-4 2000 Coexpression of HIR with IRS-1, IRS-2, and SHC strongly enhanced tyrosine phosphorylation of these proteins. Tyrosine 65-73 insulin receptor substrate 1 Homo sapiens 25-30 10866039-5 2000 A similar increase in tyrosine phosphorylation was observed in cells overexpressing IRS-1, IRS-2, or SHC together with all HIR mutants except HIR delta JM and a mutant carrying exchanges of serines 1177, 1178, and 1182 to alanine (HIR1177/78/82), although this mutant showed normal autophosphorylation. Tyrosine 22-30 insulin receptor substrate 1 Homo sapiens 84-89 10866039-8 2000 Again, HIR1177/78/82 showed normal autophosphorylation but showed a clear decrease in tyrosine phosphorylation of endogenous IRS-1 and activation of PI 3-kinase. Tyrosine 86-94 insulin receptor substrate 1 Homo sapiens 125-130 10777546-6 2000 Analysis of tyrosine-phosphorylated insulin receptor substrate-1 showed that the highest levels were found in cells stimulated by estradiol and insulin-like growth factor-I, whereas low levels were found in the absence of estradiol irrespective of whether type I insulin-like growth factor ligands were present. Tyrosine 12-20 insulin receptor substrate 1 Homo sapiens 36-64 10726921-9 2000 In muscle obtained during clamp studies prior to vanadium therapy, insulin stimulated the tyrosine phosphorylation of the insulin receptor, insulin receptor substrate-1 (IRS-1), and Shc proteins by 2- to 3-fold, while phosphatidylinositol 3-kinase (PI 3-kinase) activity associated with IRS-1 increased 4.7-fold during insulin stimulation (P = .02). Tyrosine 90-98 insulin receptor substrate 1 Homo sapiens 170-175 10726921-10 2000 Following vanadium, there was a consistent trend for increased basal levels of insulin receptor, Shc, and IRS-1 protein tyrosine phosphorylation and IRS-1-associated PI 3-kinase, but no further increase with insulin. Tyrosine 120-128 insulin receptor substrate 1 Homo sapiens 106-111 10543935-3 1999 While IGF-I caused tyrosine phosphorylation of IRS-1 in both transfected cell lines, increased MAP kinase activity was not seen. Tyrosine 19-27 insulin receptor substrate 1 Homo sapiens 47-52 10092613-0 1999 Modulation of insulin receptor substrate-1 tyrosine phosphorylation by an Akt/phosphatidylinositol 3-kinase pathway. Tyrosine 43-51 insulin receptor substrate 1 Homo sapiens 14-42 10319328-3 1999 Estrogen induction of IGFR1 and IRS expression resulted in enhanced tyrosine phosphorylation of IRS-1 after IGF-I stimulation, followed by enhanced mitogen-activated protein kinase activation. Tyrosine 68-76 insulin receptor substrate 1 Homo sapiens 96-101 10087274-9 1999 However, both the tyrosine phosphorylation of insulin receptor substrate-1 and its association with phosphatidylinositol 3-kinase were enhanced in cells cultured on BM, as was the phosphorylation of the phosphatidylinositol 3-kinase effector, protein kinase B. Tyrosine 18-26 insulin receptor substrate 1 Homo sapiens 46-74 9932214-3 1998 The binding of insulin to its receptor induces autophosphorylation of the receptor on tyrosine residues and thereby stimulates its tyrosine kinase activity towards intracellular substrates such as Shc or IRS1. Tyrosine 86-94 insulin receptor substrate 1 Homo sapiens 204-208 10037694-1 1999 Phosphotyrosine binding (PTB) domains of the adaptor protein Shc and insulin receptor substrate (IRS-1) interact with a distinct set of activated and tyrosine-phosphorylated cytokine and growth factor receptors and play important roles in mediating mitogenic signal transduction. Tyrosine 7-15 insulin receptor substrate 1 Homo sapiens 97-102 10037694-2 1999 By using the technique of isothermal titration calorimetry, we have studied the thermodynamics of binding of the Shc and IRS-1 PTB domains to tyrosine-phosphorylated NPXY-containing peptides derived from known receptor binding sites. Tyrosine 142-150 insulin receptor substrate 1 Homo sapiens 121-126 10037694-6 1999 Mutagenesis and amino acid substitution experiments showed that in addition to the tyrosine-phosphorylated NPXY motif, the PTB domains of Shc and IRS-1 prefer a large hydrophobic residue at pY-5 and a small hydrophobic residue at pY-1, respectively (where pY is phosphotyrosine). Tyrosine 83-91 insulin receptor substrate 1 Homo sapiens 146-151 10037694-7 1999 These results agree with the calculated solvent accessibility of these two key peptide residues in the PTB domain/peptide structures and support the notion that the PTB domains of Shc and IRS-1 employ functionally distinct mechanisms to recognize tyrosine-phosphorylated receptors. Tyrosine 247-255 insulin receptor substrate 1 Homo sapiens 188-193 9878535-5 1998 The severe IRS-1 deficiency in MCF-7 cells was associated with (1) reduced mitogenic response to 20 ng/ml insulin and 10% calf serum (CS), but not to 1 nM estradiol (E2); (2) loss of insulin-E2 synergism; (3) up-regulation of ER protein expression and binding capacity; and (4) loss of insulin-induced regulation of ER tyrosine phosphorylation. Tyrosine 319-327 insulin receptor substrate 1 Homo sapiens 11-16 10395191-6 1999 A reduction in tyrosine phosphorylation of both the insulin receptor (IR) and the insulin receptor substrate-1 (IRS-1) has been noted in both animal and human type 2 diabetes. Tyrosine 15-23 insulin receptor substrate 1 Homo sapiens 82-110 10395191-6 1999 A reduction in tyrosine phosphorylation of both the insulin receptor (IR) and the insulin receptor substrate-1 (IRS-1) has been noted in both animal and human type 2 diabetes. Tyrosine 15-23 insulin receptor substrate 1 Homo sapiens 112-117 10453987-5 1999 We demonstrated tyrosine phosphorylation of IRS-1/2 immunoprecipitated from MG-63 cells stimulated with IGF-I. Tyrosine 16-24 insulin receptor substrate 1 Homo sapiens 44-49 9832428-5 1998 In a first series of experiments using the yeast two-hybrid system, we show that IRS-1 interacts with p85alpha, and this interaction depends on tyrosine phosphorylation, as shown with the IRS-1 mutant F18 and 3Y-IRS-1. Tyrosine 144-152 insulin receptor substrate 1 Homo sapiens 81-86 9832428-6 1998 F18-IRS-1 contains 18 potential tyrosine phosphorylation sites mutated to phenylalanine; three of them, i.e. Y608, 628, and 658, which are potential binding sites for p85alpha, have been added back in the 3Y-IRS-1 mutant. Tyrosine 32-40 insulin receptor substrate 1 Homo sapiens 4-9 9832428-7 1998 The tyrosine phosphorylation of IRS-1, which is required for the interaction with p85alpha, is thought to occur via endogenous yeast kinases that phosphorylate IRS-1 at least on these PI 3-kinase-binding sites. Tyrosine 4-12 insulin receptor substrate 1 Homo sapiens 32-37 9832428-7 1998 The tyrosine phosphorylation of IRS-1, which is required for the interaction with p85alpha, is thought to occur via endogenous yeast kinases that phosphorylate IRS-1 at least on these PI 3-kinase-binding sites. Tyrosine 4-12 insulin receptor substrate 1 Homo sapiens 160-165 9849961-2 1998 We show here that insulin receptor substrate-1 (IRS-1) phosphorylation on tyrosine and serine residues and association with phosphatidylinositol 3-kinase (PI 3-kinase) are also associated with IGF-dependent myogenic differentiation. Tyrosine 74-82 insulin receptor substrate 1 Homo sapiens 18-46 9849961-2 1998 We show here that insulin receptor substrate-1 (IRS-1) phosphorylation on tyrosine and serine residues and association with phosphatidylinositol 3-kinase (PI 3-kinase) are also associated with IGF-dependent myogenic differentiation. Tyrosine 74-82 insulin receptor substrate 1 Homo sapiens 48-53 9753293-5 1998 Insulin stimulation of insulin receptor substrate (IRS) 1 tyrosine phosphorylation and the association of IRS-1 with phosphatidylinositol (PI) 3-kinase were not impaired by oxidative stress. Tyrosine 58-66 insulin receptor substrate 1 Homo sapiens 23-57 9792713-1 1998 Signaling through the insulin receptor tyrosine kinase involves its autophosphorylation in response to insulin and the subsequent tyrosine phosphorylation of substrate proteins such as insulin receptor substrate-1 (IRS-1). Tyrosine 39-47 insulin receptor substrate 1 Homo sapiens 185-213 9792713-1 1998 Signaling through the insulin receptor tyrosine kinase involves its autophosphorylation in response to insulin and the subsequent tyrosine phosphorylation of substrate proteins such as insulin receptor substrate-1 (IRS-1). Tyrosine 39-47 insulin receptor substrate 1 Homo sapiens 215-220 9833943-9 1998 Similarly, insulin was two to three times more effective in stimulating tyrosine phosphorylation of IRS-1 in subcutaneous fat cells (p < 0.01). Tyrosine 72-80 insulin receptor substrate 1 Homo sapiens 100-105 9822703-1 1998 Insulin receptor substrate-1 (IRS-1) is a major substrate of insulin and insulin-like growth factor-I receptors, which upon phosphorylation on tyrosine docks several signaling molecules. Tyrosine 143-151 insulin receptor substrate 1 Homo sapiens 0-28 9822703-1 1998 Insulin receptor substrate-1 (IRS-1) is a major substrate of insulin and insulin-like growth factor-I receptors, which upon phosphorylation on tyrosine docks several signaling molecules. Tyrosine 143-151 insulin receptor substrate 1 Homo sapiens 30-35 9822703-8 1998 When IRS-1 was expressed in 293 cells together with pp125(FAK) or Src, we found extensive IRS-1 tyrosine phosphorylation. Tyrosine 96-104 insulin receptor substrate 1 Homo sapiens 5-10 9822703-8 1998 When IRS-1 was expressed in 293 cells together with pp125(FAK) or Src, we found extensive IRS-1 tyrosine phosphorylation. Tyrosine 96-104 insulin receptor substrate 1 Homo sapiens 90-95 9822703-12 1998 Moreover, we found that engagement of integrins induced IRS-1 tyrosine phosphorylation. Tyrosine 62-70 insulin receptor substrate 1 Homo sapiens 56-61 9545332-3 1998 Mutation of the central Tyr497 to Phe blocks the tyrosine phosphorylation of the insulin receptor substrate 1 (IRS1) and diminishes proliferation in response to IL-4. Tyrosine 49-57 insulin receptor substrate 1 Homo sapiens 81-109 9760308-7 1998 The signal generated by the insulin receptor, as reflected in the extent of insulin receptor substrate-1 tyrosine phosphorylation, was unchanged after the exercise. Tyrosine 105-113 insulin receptor substrate 1 Homo sapiens 76-104 9685425-7 1998 Reduction of intracellular ATP using azide inhibited Glut 1 and Glut 4 translocation from the LDM to the plasma membrane, insulin receptor autophosphorylation, and IRS-1 tyrosine phosphorylation. Tyrosine 170-178 insulin receptor substrate 1 Homo sapiens 164-169 9671232-8 1998 Next, we studied insulin receptor substrate-1 (IRS-1), a major endogenous substrate for the insulin receptor which, when tyrosine is phosphorylated by the insulin receptor, interacts with and activates PI3-K. Tyrosine 121-129 insulin receptor substrate 1 Homo sapiens 17-45 9671232-8 1998 Next, we studied insulin receptor substrate-1 (IRS-1), a major endogenous substrate for the insulin receptor which, when tyrosine is phosphorylated by the insulin receptor, interacts with and activates PI3-K. Tyrosine 121-129 insulin receptor substrate 1 Homo sapiens 47-52 9578588-10 1998 In addition, PI3-k activation was detected in IRS-1 immunoprecipitates from VS-stimulated cells, indicating that tyrosine-phosphorylated IRS-1 was able to interact and thereby activate PI3-k in response to VS. Taken together, these results provide evidence that tyrosine phosphorylation of IRS-1 and activation of PI3-k play a key role in mediating the insulinomimetic effect of VS on glycogen synthesis independent of IR-tyrosine phosphorylation. Tyrosine 113-121 insulin receptor substrate 1 Homo sapiens 46-51 9578588-10 1998 In addition, PI3-k activation was detected in IRS-1 immunoprecipitates from VS-stimulated cells, indicating that tyrosine-phosphorylated IRS-1 was able to interact and thereby activate PI3-k in response to VS. Taken together, these results provide evidence that tyrosine phosphorylation of IRS-1 and activation of PI3-k play a key role in mediating the insulinomimetic effect of VS on glycogen synthesis independent of IR-tyrosine phosphorylation. Tyrosine 113-121 insulin receptor substrate 1 Homo sapiens 137-142 9578588-10 1998 In addition, PI3-k activation was detected in IRS-1 immunoprecipitates from VS-stimulated cells, indicating that tyrosine-phosphorylated IRS-1 was able to interact and thereby activate PI3-k in response to VS. Taken together, these results provide evidence that tyrosine phosphorylation of IRS-1 and activation of PI3-k play a key role in mediating the insulinomimetic effect of VS on glycogen synthesis independent of IR-tyrosine phosphorylation. Tyrosine 113-121 insulin receptor substrate 1 Homo sapiens 137-142 9578588-10 1998 In addition, PI3-k activation was detected in IRS-1 immunoprecipitates from VS-stimulated cells, indicating that tyrosine-phosphorylated IRS-1 was able to interact and thereby activate PI3-k in response to VS. Taken together, these results provide evidence that tyrosine phosphorylation of IRS-1 and activation of PI3-k play a key role in mediating the insulinomimetic effect of VS on glycogen synthesis independent of IR-tyrosine phosphorylation. Tyrosine 262-270 insulin receptor substrate 1 Homo sapiens 46-51 9578588-10 1998 In addition, PI3-k activation was detected in IRS-1 immunoprecipitates from VS-stimulated cells, indicating that tyrosine-phosphorylated IRS-1 was able to interact and thereby activate PI3-k in response to VS. Taken together, these results provide evidence that tyrosine phosphorylation of IRS-1 and activation of PI3-k play a key role in mediating the insulinomimetic effect of VS on glycogen synthesis independent of IR-tyrosine phosphorylation. Tyrosine 262-270 insulin receptor substrate 1 Homo sapiens 137-142 9578588-10 1998 In addition, PI3-k activation was detected in IRS-1 immunoprecipitates from VS-stimulated cells, indicating that tyrosine-phosphorylated IRS-1 was able to interact and thereby activate PI3-k in response to VS. Taken together, these results provide evidence that tyrosine phosphorylation of IRS-1 and activation of PI3-k play a key role in mediating the insulinomimetic effect of VS on glycogen synthesis independent of IR-tyrosine phosphorylation. Tyrosine 262-270 insulin receptor substrate 1 Homo sapiens 137-142 9578588-10 1998 In addition, PI3-k activation was detected in IRS-1 immunoprecipitates from VS-stimulated cells, indicating that tyrosine-phosphorylated IRS-1 was able to interact and thereby activate PI3-k in response to VS. Taken together, these results provide evidence that tyrosine phosphorylation of IRS-1 and activation of PI3-k play a key role in mediating the insulinomimetic effect of VS on glycogen synthesis independent of IR-tyrosine phosphorylation. Tyrosine 262-270 insulin receptor substrate 1 Homo sapiens 46-51 9578588-10 1998 In addition, PI3-k activation was detected in IRS-1 immunoprecipitates from VS-stimulated cells, indicating that tyrosine-phosphorylated IRS-1 was able to interact and thereby activate PI3-k in response to VS. Taken together, these results provide evidence that tyrosine phosphorylation of IRS-1 and activation of PI3-k play a key role in mediating the insulinomimetic effect of VS on glycogen synthesis independent of IR-tyrosine phosphorylation. Tyrosine 262-270 insulin receptor substrate 1 Homo sapiens 137-142 9578588-10 1998 In addition, PI3-k activation was detected in IRS-1 immunoprecipitates from VS-stimulated cells, indicating that tyrosine-phosphorylated IRS-1 was able to interact and thereby activate PI3-k in response to VS. Taken together, these results provide evidence that tyrosine phosphorylation of IRS-1 and activation of PI3-k play a key role in mediating the insulinomimetic effect of VS on glycogen synthesis independent of IR-tyrosine phosphorylation. Tyrosine 262-270 insulin receptor substrate 1 Homo sapiens 137-142 9609124-5 1998 Impaired insulin-stimulated GLUT4 translocation and glucose transport in NIDDM skeletal muscle is associated with reduced insulin-stimulated IRS-1 tyrosine phosphorylation and PI3-kinase activity. Tyrosine 147-155 insulin receptor substrate 1 Homo sapiens 141-146 9545345-3 1998 IGF-I, insulin, and IL-4 treatment of MCF-7 and ZR-75, and IGF-I treatment of T47-D breast cancer cells, resulted in much greater tyrosine phosphorylation of IRS-1 compared with IRS-2. Tyrosine 130-138 insulin receptor substrate 1 Homo sapiens 158-163 9545345-4 1998 Furthermore, IGF-I stimulated greater tyrosine phosphorylation of IRS-1 than either insulin or IL-4. Tyrosine 38-46 insulin receptor substrate 1 Homo sapiens 66-71 9545345-10 1998 Furthermore, enhanced tyrosine phosphorylation of IRS-1 by IGF-I, compared with either insulin or IL-4, is associated with greater activation of mitogenic downstream signaling pathways resulting in enhanced cell growth. Tyrosine 22-30 insulin receptor substrate 1 Homo sapiens 50-55 9545332-3 1998 Mutation of the central Tyr497 to Phe blocks the tyrosine phosphorylation of the insulin receptor substrate 1 (IRS1) and diminishes proliferation in response to IL-4. Tyrosine 49-57 insulin receptor substrate 1 Homo sapiens 111-115 9545332-4 1998 Recent data suggest that the I4R motif encodes binding sites for several protein tyrosine binding (PTB) domain-containing proteins such as IRS1 and Shc and potentially for the Src homology 2 domain of signal transducer and activator of transcription 6 (STAT6). Tyrosine 81-89 insulin receptor substrate 1 Homo sapiens 139-143 9421370-7 1998 Incubation for 24 h with tumor necrosis factor-alpha (TNF-alpha) but not C2-ceramide decreased the concentration and insulin-induced tyrosine phosphorylation of IRS-1 in this experimental system. Tyrosine 133-141 insulin receptor substrate 1 Homo sapiens 161-166 9568681-7 1998 The inhibitory action of TNF-alpha was dose-dependent, already detectable at 10 pmol/l, and was correlated to inhibition of tyrosine phosphorylation of IRS-1 with an unaltered autophosphorylation of the insulin receptor beta-subunit. Tyrosine 124-132 insulin receptor substrate 1 Homo sapiens 152-157 9565570-4 1998 Insulin stimulation induces rapid tyrosine phosphorylation of both IRS-1 and IRS-2. Tyrosine 34-42 insulin receptor substrate 1 Homo sapiens 67-72 9492043-5 1998 Similarly, wild-type p53 decreased IGF-I-induced tyrosine phosphorylation of IRS-1. Tyrosine 49-57 insulin receptor substrate 1 Homo sapiens 77-82 9422724-4 1998 Bisphosphorylated TAMs (tyrosine-based activation motifs) were derived from biologically relevant sites in platelet-derived growth factor, T cell, B cell, and high affinity IgE receptors and the receptor substrates IRS-1 (insulin receptor substrate-1) and SHPS-1/SIRP. Tyrosine 24-32 insulin receptor substrate 1 Homo sapiens 215-220 9422724-4 1998 Bisphosphorylated TAMs (tyrosine-based activation motifs) were derived from biologically relevant sites in platelet-derived growth factor, T cell, B cell, and high affinity IgE receptors and the receptor substrates IRS-1 (insulin receptor substrate-1) and SHPS-1/SIRP. Tyrosine 24-32 insulin receptor substrate 1 Homo sapiens 222-250 9395471-0 1997 Modulation of insulin receptor substrate-1 tyrosine phosphorylation and function by mitogen-activated protein kinase. Tyrosine 43-51 insulin receptor substrate 1 Homo sapiens 14-42 9395471-1 1997 Increased serine phosphorylation of insulin receptor substrate-1 (IRS-1) has been observed in several systems to correlate with a decreased ability of the insulin receptor to tyrosine-phosphorylate this endogenous substrate and to inhibit its subsequent association with phosphatidylinositol 3-kinase. Tyrosine 175-183 insulin receptor substrate 1 Homo sapiens 36-64 9395471-1 1997 Increased serine phosphorylation of insulin receptor substrate-1 (IRS-1) has been observed in several systems to correlate with a decreased ability of the insulin receptor to tyrosine-phosphorylate this endogenous substrate and to inhibit its subsequent association with phosphatidylinositol 3-kinase. Tyrosine 175-183 insulin receptor substrate 1 Homo sapiens 66-71 9395471-3 1997 First, recombinantly produced kinase was shown to phosphorylate intact IRS-1 in a way that decreased the ability of isolated insulin receptor to phosphorylate the tyrosines recognized by the SH2 domains of the phosphatidylinositol 3-kinase. Tyrosine 163-172 insulin receptor substrate 1 Homo sapiens 71-76 9395471-8 1997 These studies implicate MAP kinase as one of the kinases capable of phosphorylating and regulating IRS-1 tyrosine phosphorylation. Tyrosine 105-113 insulin receptor substrate 1 Homo sapiens 99-104 9374504-4 1997 Although at low concentrations of insulin, the mutant receptors were impaired in their ability to stimulate the tyrosine phosphorylation of IRS-1, at higher insulin concentrations we confirmed that the cells expressing the mutant receptors showed significantly increased tyrosine phosphorylation of IRS-1 compared with parental nontransfected cells. Tyrosine 112-120 insulin receptor substrate 1 Homo sapiens 140-145 9415826-1 1997 Insulin binding to its receptor activates a tyrosine kinase that initiates a cascade of signaling events, the initial step being the tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1). Tyrosine 44-52 insulin receptor substrate 1 Homo sapiens 161-189 9415826-1 1997 Insulin binding to its receptor activates a tyrosine kinase that initiates a cascade of signaling events, the initial step being the tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1). Tyrosine 44-52 insulin receptor substrate 1 Homo sapiens 191-196 9374521-0 1997 Insulin receptor substrate (IRS)-1 and IRS-2 are tyrosine-phosphorylated and associated with phosphatidylinositol 3-kinase in response to brain-derived neurotrophic factor in cultured cerebral cortical neurons. Tyrosine 49-57 insulin receptor substrate 1 Homo sapiens 0-34 9374521-5 1997 We found that insulin receptor substrate (IRS)-1 and -2 are involved in the BDNF signaling pathway that activates PI3-K. IRS-1 and -2 were tyrosine-phosphorylated and bound to PI3-K in response to BDNF. Tyrosine 139-147 insulin receptor substrate 1 Homo sapiens 14-55 9374521-5 1997 We found that insulin receptor substrate (IRS)-1 and -2 are involved in the BDNF signaling pathway that activates PI3-K. IRS-1 and -2 were tyrosine-phosphorylated and bound to PI3-K in response to BDNF. Tyrosine 139-147 insulin receptor substrate 1 Homo sapiens 121-133 9374504-4 1997 Although at low concentrations of insulin, the mutant receptors were impaired in their ability to stimulate the tyrosine phosphorylation of IRS-1, at higher insulin concentrations we confirmed that the cells expressing the mutant receptors showed significantly increased tyrosine phosphorylation of IRS-1 compared with parental nontransfected cells. Tyrosine 271-279 insulin receptor substrate 1 Homo sapiens 140-145 9374504-4 1997 Although at low concentrations of insulin, the mutant receptors were impaired in their ability to stimulate the tyrosine phosphorylation of IRS-1, at higher insulin concentrations we confirmed that the cells expressing the mutant receptors showed significantly increased tyrosine phosphorylation of IRS-1 compared with parental nontransfected cells. Tyrosine 271-279 insulin receptor substrate 1 Homo sapiens 299-304 9346913-3 1997 Chimeric IRS-1 proteins containing a homologous PH domain derived from other IRS proteins (IRS-2 or Gab-1) were tyrosine phosphorylated normally in response to insulin. Tyrosine 112-120 insulin receptor substrate 1 Homo sapiens 9-14 9356025-5 1997 Prior exercise caused significantly faster insulin-stimulated tyrosine phosphorylation of IRS-1, PI 3-kinase activity, and glucose clearance compared with those in the rested thigh. Tyrosine 62-70 insulin receptor substrate 1 Homo sapiens 90-95 9346913-6 1997 Thus, tyrosine phosphorylation of IRS-1 by the insulin receptor specifically requires a PH domain derived from IRS proteins. Tyrosine 6-14 insulin receptor substrate 1 Homo sapiens 34-39 9312188-5 1997 Troglitazone or pioglitazone essentially eliminate the reduction in tyrosine phosphorylation of IR and IRS-1 caused by TNF-alpha in fat cells, even at relatively high doses (25 ng/ml). Tyrosine 68-76 insulin receptor substrate 1 Homo sapiens 103-108 9335553-0 1997 Protein kinase C modulation of insulin receptor substrate-1 tyrosine phosphorylation requires serine 612. Tyrosine 60-68 insulin receptor substrate 1 Homo sapiens 31-59 9335553-1 1997 Activation of the endogenous protein kinase Cs in human kidney fibroblast (293) cells was found in the present study to inhibit the subsequent ability of insulin to stimulate the tyrosine phosphorylation of an expressed insulin receptor substrate-1. Tyrosine 179-187 insulin receptor substrate 1 Homo sapiens 220-248 9345317-1 1997 Two early events downstream of insulin receptor autophosphorylation that are necessary for activation of glucose transport in adipocytes appear to be: (1) The tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) which (2) recruits and activates phosphatidylinositol 3"-kinase (PI3"-K). Tyrosine 159-167 insulin receptor substrate 1 Homo sapiens 187-215 9345317-1 1997 Two early events downstream of insulin receptor autophosphorylation that are necessary for activation of glucose transport in adipocytes appear to be: (1) The tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) which (2) recruits and activates phosphatidylinositol 3"-kinase (PI3"-K). Tyrosine 159-167 insulin receptor substrate 1 Homo sapiens 217-222 9312143-10 1997 Phosphoamino acid analysis revealed that IRS-1 coimmunoprecipitated with anti-14-3-3 antibody to be weakly phosphorylated after insulin stimulation, on tyrosine as well as serine residues, compared with IRS-1 immunoprecipitated with anti-IRS-1 antibody. Tyrosine 152-160 insulin receptor substrate 1 Homo sapiens 41-46 9295312-8 1997 Affinity chromatography of phosphopeptide libraries using the glutathione S-transferase fusion protein of the C terminus of SERCA1 indicated a consensus sequence for binding of XpYGSS; this is identical to potential tyrosine phosphorylation sites at position 431 of human IRS-1 and at position 500 of human IRS-2. Tyrosine 216-224 insulin receptor substrate 1 Homo sapiens 272-277 9139718-9 1997 In addition, we also demonstrate that IL-13 stimulates the tyrosine phosphorylation of the adaptor molecule insulin receptor substrate 1, which may facilitate receptor coupling to PtdIns 3-kinase. Tyrosine 59-67 insulin receptor substrate 1 Homo sapiens 108-136 9271396-1 1997 The ability of insulin to stimulate protein synthesis and cellular growth is mediated through the insulin receptor (IR), which phosphorylates Tyr residues in the insulin receptor substrate-signaling proteins (IRS-1 and IRS-2), Gab-1, and Shc. Tyrosine 142-145 insulin receptor substrate 1 Homo sapiens 209-214 9233603-2 1997 We demonstrate that, in addition to activation of the Jak1 and Jak3 kinases, IL-7 stimulation of human thymocytes results in the rapid tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and IRS-2 proteins. Tyrosine 135-143 insulin receptor substrate 1 Homo sapiens 163-191 9233603-2 1997 We demonstrate that, in addition to activation of the Jak1 and Jak3 kinases, IL-7 stimulation of human thymocytes results in the rapid tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and IRS-2 proteins. Tyrosine 135-143 insulin receptor substrate 1 Homo sapiens 193-198 9202037-5 1997 An in vitro association assay, performed with or without activation of tyrosine kinases, gives evidence that tyrosine phosphorylation of IRS-1 and Shc drastically improves the interaction. Tyrosine 71-79 insulin receptor substrate 1 Homo sapiens 137-142 9245714-0 1997 Tyrosine phosphorylation of insulin receptor substrate-1 and activation of the PI-3-kinase pathway by glycine-extended gastrin precursors. Tyrosine 0-8 insulin receptor substrate 1 Homo sapiens 28-56 9245714-5 1997 We also observed a rapid increase in the tyrosine phosphorylation of IRS-1 and an activation of the PI-3-kinase in anti-IRS-1 immunoprecipitates, suggesting that PI-3-kinase may be activated by association with tyrosine phosphorylated IRS-1. Tyrosine 41-49 insulin receptor substrate 1 Homo sapiens 69-74 9245714-5 1997 We also observed a rapid increase in the tyrosine phosphorylation of IRS-1 and an activation of the PI-3-kinase in anti-IRS-1 immunoprecipitates, suggesting that PI-3-kinase may be activated by association with tyrosine phosphorylated IRS-1. Tyrosine 211-219 insulin receptor substrate 1 Homo sapiens 69-74 9245714-5 1997 We also observed a rapid increase in the tyrosine phosphorylation of IRS-1 and an activation of the PI-3-kinase in anti-IRS-1 immunoprecipitates, suggesting that PI-3-kinase may be activated by association with tyrosine phosphorylated IRS-1. Tyrosine 211-219 insulin receptor substrate 1 Homo sapiens 120-125 9245714-5 1997 We also observed a rapid increase in the tyrosine phosphorylation of IRS-1 and an activation of the PI-3-kinase in anti-IRS-1 immunoprecipitates, suggesting that PI-3-kinase may be activated by association with tyrosine phosphorylated IRS-1. Tyrosine 211-219 insulin receptor substrate 1 Homo sapiens 120-125 9115260-4 1997 CSF-1 stimulated the tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and Shc in cells expressing the CSF1R/IR chimera. Tyrosine 21-29 insulin receptor substrate 1 Homo sapiens 49-77 9115260-4 1997 CSF-1 stimulated the tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and Shc in cells expressing the CSF1R/IR chimera. Tyrosine 21-29 insulin receptor substrate 1 Homo sapiens 79-84 9036989-1 1997 During engagement of the type I IFN receptor, IRS-1 is phosphorylated on tyrosine and associates with the p85 regulatory subunit of the phosphatidylinositol (PI) 3"-kinase, which is a dual-specificity enzyme possessing both lipid and serine kinase activities. Tyrosine 73-81 insulin receptor substrate 1 Homo sapiens 46-51 9100005-5 1997 Recently, we determined the solution structure of the phosphotyrosine binding (PTB) domain of the insulin receptor substrate (IRS-1) complexed to a tyrosine-phosphorylated peptide derived from the interleukin 4 (IL-4) receptor [Zhou et al., (1996) Nat. Tyrosine 61-69 insulin receptor substrate 1 Homo sapiens 126-131 9205064-10 1997 In summary, this work provides the first evidence that in MCF-7 cells, cytostatic effects of Tam are associated with the modulation of IGF-IR signaling, specifically with: (a) down-regulation of IGF-I-induced tyrosine phosphorylation of the IGF-IR; (b) inhibition of IRS-1/phosphatidylinositol 3"-kinase signaling; and (c) up-regulation of SHC tyrosine phosphorylation and increased SHC/GRB2 binding. Tyrosine 209-217 insulin receptor substrate 1 Homo sapiens 267-272 9205064-10 1997 In summary, this work provides the first evidence that in MCF-7 cells, cytostatic effects of Tam are associated with the modulation of IGF-IR signaling, specifically with: (a) down-regulation of IGF-I-induced tyrosine phosphorylation of the IGF-IR; (b) inhibition of IRS-1/phosphatidylinositol 3"-kinase signaling; and (c) up-regulation of SHC tyrosine phosphorylation and increased SHC/GRB2 binding. Tyrosine 344-352 insulin receptor substrate 1 Homo sapiens 267-272 9032113-1 1997 We examined the effect of physiological hyperinsulinemia on insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation and phosphatidylinositol (PI) 3-kinase activity in skeletal muscle from six lean-to-moderately obese NIDDM patients and six healthy subjects. Tyrosine 97-105 insulin receptor substrate 1 Homo sapiens 60-88 9032113-1 1997 We examined the effect of physiological hyperinsulinemia on insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation and phosphatidylinositol (PI) 3-kinase activity in skeletal muscle from six lean-to-moderately obese NIDDM patients and six healthy subjects. Tyrosine 97-105 insulin receptor substrate 1 Homo sapiens 90-95 9032113-2 1997 A rise in serum insulin levels from approximately 60 to approximately 650 pmol/l increased IRS-1 tyrosine phosphorylation sixfold over basal levels in control muscle (P < 0.01), whereas no significant increase was noted in NIDDM muscle. Tyrosine 97-105 insulin receptor substrate 1 Homo sapiens 91-96 9032113-6 1997 The present findings couple both reduced insulin-stimulated IRS-1 tyrosine phosphorylation and PI 3-kinase activity to the impaired insulin-stimulated glucose transport in skeletal muscle from lean-to-moderately obese NIDDM subjects. Tyrosine 66-74 insulin receptor substrate 1 Homo sapiens 60-65 9036989-3 1997 32P-labeling experiments and phosphoaminoacid analysis of immunoprecipitated IRS-1 protein demonstrated that, in addition to tyrosine phosphorylation, IFN-alpha induces its phosphorylation on serine residues. Tyrosine 125-133 insulin receptor substrate 1 Homo sapiens 77-82 9003010-3 1997 Insulin receptor substrate-1 (IRS-1) became tyrosine-phosphorylated and bound growth factor receptor-bound protein 2 (GRB2) quickly by IGF-I. Tyrosine 44-52 insulin receptor substrate 1 Homo sapiens 0-28 9003010-3 1997 Insulin receptor substrate-1 (IRS-1) became tyrosine-phosphorylated and bound growth factor receptor-bound protein 2 (GRB2) quickly by IGF-I. Tyrosine 44-52 insulin receptor substrate 1 Homo sapiens 30-35 8902843-3 1996 We examined the role of three insulin receptor tyrosine autophosphorylation domains in association of the receptor with IRS-1. Tyrosine 47-55 insulin receptor substrate 1 Homo sapiens 120-125 8999820-7 1997 This tyrosine residue in the context of the NDYY motif may define a novel recognition site for IRS-1. Tyrosine 5-13 insulin receptor substrate 1 Homo sapiens 95-100 8940353-1 1996 Prior studies have demonstrated that a juxtamembrane tyrosine (tyrosine 972) in the insulin receptor is required for the receptor to elicit various biological responses and to stimulate the tyrosine phosphorylation of two endogenous substrates, the insulin receptor substrate-1 and the adaptor protein called Shc. Tyrosine 53-61 insulin receptor substrate 1 Homo sapiens 249-277 8940353-1 1996 Prior studies have demonstrated that a juxtamembrane tyrosine (tyrosine 972) in the insulin receptor is required for the receptor to elicit various biological responses and to stimulate the tyrosine phosphorylation of two endogenous substrates, the insulin receptor substrate-1 and the adaptor protein called Shc. Tyrosine 63-71 insulin receptor substrate 1 Homo sapiens 249-277 8940353-1 1996 Prior studies have demonstrated that a juxtamembrane tyrosine (tyrosine 972) in the insulin receptor is required for the receptor to elicit various biological responses and to stimulate the tyrosine phosphorylation of two endogenous substrates, the insulin receptor substrate-1 and the adaptor protein called Shc. Tyrosine 63-71 insulin receptor substrate 1 Homo sapiens 249-277 8943397-10 1996 This mutation has previously been shown to abrogate the tyrosine phosphorylation of IRS-1 by human IL-4. Tyrosine 56-64 insulin receptor substrate 1 Homo sapiens 84-89 8895329-1 1996 Recent data suggest involvement of the Janus tyrosine kinase-2 (JAK2) in human GH-induced tyrosine phosphorylation of the GH receptor and the insulin receptor substrates 1 and 2 (IRS-1 and IRS-2), leading to activation of the phosphatidylinositol 3-kinase and the acute insulin-like effects in primary rat adipocytes. Tyrosine 45-53 insulin receptor substrate 1 Homo sapiens 142-177 8895329-4 1996 The inhibition of lipogenesis and antilipolysis exhibited the same staurosporine dose dependency (IC50, approximately 40 nM) as inhibition of JAK2 and IRS-1 tyrosine phosphorylation as well as binding of the p85 subunit of phosphatidylinositol 3-kinase to IRS-1 and IRS-2. Tyrosine 157-165 insulin receptor substrate 1 Homo sapiens 151-156 8756554-2 1996 IGF-I rapidly stimulated beta-chain IGF-I receptor autophosphorylation, which peaked at a physiological/mitogenic concentration (1.4 nM) and also stimulated tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1). Tyrosine 157-165 insulin receptor substrate 1 Homo sapiens 185-213 8756554-3 1996 Tyrosine-phosphorylated IRS-1 bound and subsequently activated phosphatidylinositol 3-kinase by 3.5-fold, whereas the tyrosine-phosphorylated IGF-I receptor was not directly associated with the p85 subunit of the phosphatidylinositol 3-kinase. Tyrosine 0-8 insulin receptor substrate 1 Homo sapiens 24-29 8894489-2 1996 This induces the tyrosine-phosphorylation of insulin receptor substrates-1 (IRS-1) and a complex formation between IRS-1 and other proteins including GRB2, SH-PTP2, Nck, and phosphoinositide (PI) 3-kinase consisting of a regulatory 85-kDa subunit and a catalytic 110-kDa subunit. Tyrosine 17-25 insulin receptor substrate 1 Homo sapiens 45-74 8894489-2 1996 This induces the tyrosine-phosphorylation of insulin receptor substrates-1 (IRS-1) and a complex formation between IRS-1 and other proteins including GRB2, SH-PTP2, Nck, and phosphoinositide (PI) 3-kinase consisting of a regulatory 85-kDa subunit and a catalytic 110-kDa subunit. Tyrosine 17-25 insulin receptor substrate 1 Homo sapiens 76-81 8756634-2 1996 The wide variety of tyrosine phosphorylation motifs of insulin receptor substrate 1 (IRS-1), a substrate for the activated insulin receptor tyrosine kinase, may account for the multiple functions of insulin. Tyrosine 20-28 insulin receptor substrate 1 Homo sapiens 55-83 8756634-2 1996 The wide variety of tyrosine phosphorylation motifs of insulin receptor substrate 1 (IRS-1), a substrate for the activated insulin receptor tyrosine kinase, may account for the multiple functions of insulin. Tyrosine 20-28 insulin receptor substrate 1 Homo sapiens 85-90 8756634-7 1996 Although we have shown that the Csk Src homology 2 domain can bind to several tyrosine-phosphorylated proteins, including pp125FAK and paxillin, a majority of protein which bound to Csk was IRS-1 when cells were stimulated by insulin. Tyrosine 78-86 insulin receptor substrate 1 Homo sapiens 190-195 8756634-8 1996 Our data also indicated that tyrosine phosphorylation levels of IRS-1 appear to be paralleled by the dephosphorylation of the focal adhesion proteins. Tyrosine 29-37 insulin receptor substrate 1 Homo sapiens 64-69 9115849-7 1996 alpha 2-HSG inhibits insulin-induced tyrosine phosphorylation of IRS-1 and the subsequent association of GRB2, as well as Sos, with IRS-1. Tyrosine 37-45 insulin receptor substrate 1 Homo sapiens 65-70 8887653-1 1996 The phosphotyrosine interaction (PI) domains (also known as the PTB, or phosphotyrosine binding, domains) of Shc and IRS-1 are recently described domains that bind peptides phosphorylated on tyrosine residues. Tyrosine 11-19 insulin receptor substrate 1 Homo sapiens 117-122 8824290-0 1996 Gastrin stimulates tyrosine phosphorylation of insulin receptor substrate 1 and its association with Grb2 and the phosphatidylinositol 3-kinase. Tyrosine 19-27 insulin receptor substrate 1 Homo sapiens 47-75 8824290-3 1996 In the present study, we demonstrate that gastrin stimulates tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1), the major cytoplasmic substrate of the insulin receptor. Tyrosine 61-69 insulin receptor substrate 1 Homo sapiens 89-117 8824290-3 1996 In the present study, we demonstrate that gastrin stimulates tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1), the major cytoplasmic substrate of the insulin receptor. Tyrosine 61-69 insulin receptor substrate 1 Homo sapiens 119-124 8824290-5 1996 IRS-1 binds several proteins containing Src homology 2 domains through its multiple tyrosine phosphorylation sites. Tyrosine 84-92 insulin receptor substrate 1 Homo sapiens 0-5 8824290-7 1996 In addition, activation of PI 3-kinase was detected in anti-IRS-1 immunoprecipitates from gastrin-treated cells, suggesting that tyrosine phosphorylation of IRS-1, which leads to the rapid recruitment of p85, might be one mechanism used by gastrin to activate PI 3-kinase. Tyrosine 129-137 insulin receptor substrate 1 Homo sapiens 60-65 8824290-7 1996 In addition, activation of PI 3-kinase was detected in anti-IRS-1 immunoprecipitates from gastrin-treated cells, suggesting that tyrosine phosphorylation of IRS-1, which leads to the rapid recruitment of p85, might be one mechanism used by gastrin to activate PI 3-kinase. Tyrosine 129-137 insulin receptor substrate 1 Homo sapiens 157-162 8824290-9 1996 We report here that Grb2 also interacts with tyrosine-phosphorylated IRS-1 in response to gastrin. Tyrosine 45-53 insulin receptor substrate 1 Homo sapiens 69-74 8810325-3 1996 Insulin stimulation resulted in co-immunoprecipitation of tyrosine-phosphorylated IRS1 with Grb2 and to a lesser extent CrkII. Tyrosine 58-66 insulin receptor substrate 1 Homo sapiens 82-86 8828504-2 1996 Insulin and IGF-1 stimulated tyrosine phosphorylation of IRS-1 and Shc in a similar dose- and time-dependent manner. Tyrosine 29-37 insulin receptor substrate 1 Homo sapiens 57-62 8902843-4 1996 Our data support the idea that tyrosine phosphorylation of the insulin receptor juxtamembrane domain is necessary for receptor association with IRS-1. Tyrosine 31-39 insulin receptor substrate 1 Homo sapiens 144-149 8899294-6 1996 TNF has been shown to inhibit insulin-simulated tyrosine phosphorylation of both the insulin receptor (IR) and insulin receptor substrate (IRS)-1 and to stimulate downregulation of the insulin-sensitive glucose transporter, GLUT4, in adipocytes. Tyrosine 48-56 insulin receptor substrate 1 Homo sapiens 111-145 8702728-11 1996 Insulin-induced tyrosine phosphorylation of IRS-1 was compared among the transfected cell lines, since IRS-1 and Shc could competitively interact with insulin receptor. Tyrosine 16-24 insulin receptor substrate 1 Homo sapiens 44-49 8702728-12 1996 Insulin-stimulated tyrosine phosphorylation of IRS-1 was decreased in both WT-Shc and Y317F-Shc cells compared with that in HIRc cells. Tyrosine 19-27 insulin receptor substrate 1 Homo sapiens 47-52 8649395-6 1996 Moreover, this effect requires activation of phosphatidylinositol 3-kinase (PI3K), as determined by wortmannin inhibition and the use of an IRS-1 variant lacking all Tyr residues except those which activate PI3K. Tyrosine 166-169 insulin receptor substrate 1 Homo sapiens 140-145 8713074-8 1996 The other peak was affected only slightly by G beta gamma, but was synergistically increased by G beta gamma and a tyrosine-phosphorylated peptide which was synthesized accordingly to the amino acid sequence of insulin receptor substrate-1. Tyrosine 115-123 insulin receptor substrate 1 Homo sapiens 211-239 8660383-0 1996 Differential regulation of insulin-stimulated tyrosine phosphorylation of IRS-1 and SHC by Wortmannin in intact cells. Tyrosine 46-54 insulin receptor substrate 1 Homo sapiens 74-79 8660383-2 1996 After treatment of hepatoma cells with 100 nM wortmannin, the tyrosine phosphorylation of IRS-1 in response to insulin was increased by 38.3 +/- 3.3% while its phosphoserine/threonine content was reduced by 19%. Tyrosine 62-70 insulin receptor substrate 1 Homo sapiens 90-95 8660383-3 1996 Treatment with 1 microM wortmannin further increased IRS-1 tyrosine phosphorylation to 180% of control, while under these conditions, tyrosine phosphorylation of the IR substrate p52 Shc was reduced to less than 50% of control. Tyrosine 59-67 insulin receptor substrate 1 Homo sapiens 53-58 8640952-5 1996 The level of insulin receptor substrate-1 (IRS-1) was reduced in dexamethasone-treated cells, as measured by Western blot; however, the pattern of tyrosine-phosphorylated protein subsequent to stimulation with IGF-I (1 min) was not altered. Tyrosine 147-155 insulin receptor substrate 1 Homo sapiens 13-41 8640952-10 1996 These findings indicate that the activation of MAP kinase may be dissociated from IGF-I-induced anabolic pathways and tyrosine phosphorylation of IRS-1. Tyrosine 118-126 insulin receptor substrate 1 Homo sapiens 146-151 8621421-1 1996 Multipin peptide synthesis has been employed to produce biotinylated 11-mer phosphopeptides that account for every tyrosine residue in insulin receptor substrate-1 (IRS-1) and the cytoplasmic domains of the insulin-, epidermal growth factor-, platelet-derived growth factor- and basic fibroblast growth factor receptors. Tyrosine 115-123 insulin receptor substrate 1 Homo sapiens 135-163 8626671-2 1996 In addition, this drug induces on insulin receptor substrate-1 (IRS-1) a decrease in tyrosine phosphorylation, concomitantly with an increase in serine/threonine phosphorylation. Tyrosine 85-93 insulin receptor substrate 1 Homo sapiens 34-62 8626671-2 1996 In addition, this drug induces on insulin receptor substrate-1 (IRS-1) a decrease in tyrosine phosphorylation, concomitantly with an increase in serine/threonine phosphorylation. Tyrosine 85-93 insulin receptor substrate 1 Homo sapiens 64-69 8626671-7 1996 Rather, these serines appear to play a role in modulating basal and insulin-stimulated IRS-1 tyrosine phosphorylation, association of IRS-1, with p85, and phosphatidylinositol 3-kinase activity in the IRS-1.p85 immune complex, since mutation of these sites enhances these events. Tyrosine 93-101 insulin receptor substrate 1 Homo sapiens 87-92 8645156-0 1996 Growth inhibition signalled through the interleukin-4/interleukin-13 receptor complex is associated with tyrosine phosphorylation of insulin receptor substrate-1. Tyrosine 105-113 insulin receptor substrate 1 Homo sapiens 133-161 8645156-6 1996 The present study demonstrates the involvement of a novel chain other than the gama-chain in the receptor complexes of IL-4 and IL-13 and and post-receptor tyrosine phosphorylation of IRS-1. Tyrosine 156-164 insulin receptor substrate 1 Homo sapiens 184-189 8732688-6 1996 After stimulation with 100 nM insulin, tyrosine phosphorylation of the insulin receptor was decreased by 31% at 1 min (P < 0.01) and by 42% at 10 min (P < 0.01), and that of IRS-1 was decreased by 34% (P < 0.01) at 1 min and by 56% (P < 0.01) at 10 min in the LAR-overexpressing cells compared with empty vector transfectants. Tyrosine 39-47 insulin receptor substrate 1 Homo sapiens 180-185 8599766-1 1996 We present the NMR structure of the PTB domain of insulin receptor substrate-1 (IRS-1) complexed to a tyrosine-phosphorylated peptide derived from the IL-4 receptor. Tyrosine 102-110 insulin receptor substrate 1 Homo sapiens 50-78 8599766-1 1996 We present the NMR structure of the PTB domain of insulin receptor substrate-1 (IRS-1) complexed to a tyrosine-phosphorylated peptide derived from the IL-4 receptor. Tyrosine 102-110 insulin receptor substrate 1 Homo sapiens 80-85 8626379-4 1996 The IH2PTB binds to the phosphorylated NPXY motif (Tyr-960) in the activated insulin receptor, providing a specific mechanism for the interaction between the receptor and IRS-1. Tyrosine 51-54 insulin receptor substrate 1 Homo sapiens 171-176 8621421-1 1996 Multipin peptide synthesis has been employed to produce biotinylated 11-mer phosphopeptides that account for every tyrosine residue in insulin receptor substrate-1 (IRS-1) and the cytoplasmic domains of the insulin-, epidermal growth factor-, platelet-derived growth factor- and basic fibroblast growth factor receptors. Tyrosine 115-123 insulin receptor substrate 1 Homo sapiens 165-170 8621421-3 1996 The data revealed new potential Grb2 binding sites at Tyr-1114 (epidermal growth factor receptor (EGFR) C-tail); Tyr-743 (platelet-derived growth factor receptor (PDGFR) insert region), Tyr-1110 from the E-helix of the catalytic domain of insulin receptor (IR), and Tyr-47, Tyr-939, and Tyr-727 in IRS-1. Tyrosine 54-57 insulin receptor substrate 1 Homo sapiens 298-303 8621421-5 1996 Tyr-1068 and -1086 from the C-tail of EGFR, Tyr-684 from the kinase insert region of PDGFR, and Tyr-895 from IRS-1 were confirmed as major binding sites for the Grb2 SH2 domain. Tyrosine 0-3 insulin receptor substrate 1 Homo sapiens 109-114 8612625-8 1996 Similar results have been found concerning the tyrosine phosphorylation of insulin receptor substrate-1 (IRS 1). Tyrosine 47-55 insulin receptor substrate 1 Homo sapiens 75-103 8612625-8 1996 Similar results have been found concerning the tyrosine phosphorylation of insulin receptor substrate-1 (IRS 1). Tyrosine 47-55 insulin receptor substrate 1 Homo sapiens 105-110 8612625-9 1996 Tyrosine phosphorylation of both IGF-IR and IRS 1, either under basal conditions or after stimulation with growth factors, was strongly inhibited when alpha-IR3, a monoclonal antibody to IGF-IR, was added to the culture. Tyrosine 0-8 insulin receptor substrate 1 Homo sapiens 44-49 8609215-11 1996 Proportionately, the impairment of insulin receptor substrate-1 tyrosine phosphorylation is greater than that of the insulin receptor resulting in attenuated phosphatidylinositol 3-kinase activation and mitogenic signaling. Tyrosine 64-72 insulin receptor substrate 1 Homo sapiens 35-63 8626723-1 1996 Stimulation of the insulin receptor (IR) results in tyrosine phosphorylation of the intermediate molecules insulin receptor substrate-1 (IRS-1), IRS-2, and Shc, which then couple the IR to downstream signaling pathways by serving as binding sites for signaling molecules with SH2 domains. Tyrosine 52-60 insulin receptor substrate 1 Homo sapiens 107-135 8626723-1 1996 Stimulation of the insulin receptor (IR) results in tyrosine phosphorylation of the intermediate molecules insulin receptor substrate-1 (IRS-1), IRS-2, and Shc, which then couple the IR to downstream signaling pathways by serving as binding sites for signaling molecules with SH2 domains. Tyrosine 52-60 insulin receptor substrate 1 Homo sapiens 137-142 8626723-2 1996 It has been proposed that direct binding of IRS-1, IRS-2, and Shc to an NPX-Tyr(P) motif in the juxtamembrane region of the IR is required for tyrosine phosphorylation of these molecules by the IR. Tyrosine 76-79 insulin receptor substrate 1 Homo sapiens 44-49 8626723-2 1996 It has been proposed that direct binding of IRS-1, IRS-2, and Shc to an NPX-Tyr(P) motif in the juxtamembrane region of the IR is required for tyrosine phosphorylation of these molecules by the IR. Tyrosine 143-151 insulin receptor substrate 1 Homo sapiens 44-49 8621421-5 1996 Tyr-1068 and -1086 from the C-tail of EGFR, Tyr-684 from the kinase insert region of PDGFR, and Tyr-895 from IRS-1 were confirmed as major binding sites for the Grb2 SH2 domain. Tyrosine 44-47 insulin receptor substrate 1 Homo sapiens 109-114 8621421-5 1996 Tyr-1068 and -1086 from the C-tail of EGFR, Tyr-684 from the kinase insert region of PDGFR, and Tyr-895 from IRS-1 were confirmed as major binding sites for the Grb2 SH2 domain. Tyrosine 44-47 insulin receptor substrate 1 Homo sapiens 109-114 7559478-1 1995 Insulin receptor substrate 1 (IRS-1) and src homology and collagen protein (SHC) are signaling proteins which are rapidly phosphorylated on tyrosines after insulin receptor (IR) activation. Tyrosine 140-149 insulin receptor substrate 1 Homo sapiens 0-28 8557683-7 1996 Insulin-dependent tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) and Shc was 3-fold greater in CD45- cells. Tyrosine 18-26 insulin receptor substrate 1 Homo sapiens 46-74 8557683-7 1996 Insulin-dependent tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) and Shc was 3-fold greater in CD45- cells. Tyrosine 18-26 insulin receptor substrate 1 Homo sapiens 76-81 8550552-5 1996 Tyr-950 together with its surrounding sequence is involved in mediating the interaction between the gag-IGFR and insulin receptor substrate 1. Tyrosine 0-3 insulin receptor substrate 1 Homo sapiens 113-141 8983814-5 1996 IRS-1 binds several Src homology 2 (SH2) proteins through its multiple tyrosine phosphorylation sites: phosphatidylinositol 3-kinase (PI 3-kinase), the Ras guanine-nucleotide-releasing complex Grb2-SOS, the tyrosine phosphatase Syp, and the adapter protein Nck. Tyrosine 71-79 insulin receptor substrate 1 Homo sapiens 0-5 15157524-1 1996 The insulin receptor is a transmembrane tyrosine kinase that is essential for mediating multiple intracellular signalling cascades that lead ultimately to the biological actions of insulin Tyrosine phosphorylation o f the cytosolic proteins insulin receptor substrate 1 and 2 (IRS1 and IRS2) produces protein "scaffolding" for the assembly of effector proteins containing Src homology 2 (SH2) domains, thereby generating multisubunit signalling complexes. Tyrosine 189-197 insulin receptor substrate 1 Homo sapiens 277-281 7492780-7 1995 Enhanced tyrosine phosphorylation of IRS-1/4PS was observed in response to IL-4, but not IL-13 treatment of L cells transfected with the IL-2R gamma chain. Tyrosine 9-17 insulin receptor substrate 1 Homo sapiens 37-42 7588273-0 1995 Identification by mutation of the tyrosine residues in the insulin receptor substrate-1 affecting association with the tyrosine phosphatase 2C and phosphatidylinositol 3-kinase. Tyrosine 34-42 insulin receptor substrate 1 Homo sapiens 59-87 7588273-1 1995 The insulin receptor substrate-1 (IRS-1) is rapidly phosphorylated on several tyrosine residues by the activated insulin receptor. Tyrosine 78-86 insulin receptor substrate 1 Homo sapiens 4-32 7588273-1 1995 The insulin receptor substrate-1 (IRS-1) is rapidly phosphorylated on several tyrosine residues by the activated insulin receptor. Tyrosine 78-86 insulin receptor substrate 1 Homo sapiens 34-39 7588273-4 1995 In this report, we examined which tyrosine residues of IRS-1 are required for the interactions of IRS-1 with PI3-K and PTP2C. Tyrosine 34-42 insulin receptor substrate 1 Homo sapiens 55-60 7588273-4 1995 In this report, we examined which tyrosine residues of IRS-1 are required for the interactions of IRS-1 with PI3-K and PTP2C. Tyrosine 34-42 insulin receptor substrate 1 Homo sapiens 98-103 7588273-7 1995 Our results demonstrate that mutation of tyrosine 608 affects the PI3-K activity associated with IRS-1, suggesting that this tyrosine is likely to be a principal site of interaction with the SH2 domains of p85 in response to insulin. Tyrosine 41-49 insulin receptor substrate 1 Homo sapiens 97-102 7588273-7 1995 Our results demonstrate that mutation of tyrosine 608 affects the PI3-K activity associated with IRS-1, suggesting that this tyrosine is likely to be a principal site of interaction with the SH2 domains of p85 in response to insulin. Tyrosine 125-133 insulin receptor substrate 1 Homo sapiens 97-102 7588273-8 1995 Furthermore, we found that mutation of tyrosines 1172 and 1222 totally prevents the insulin-induced association of IRS-1 with the SH2 domains of PTP2C, demonstrating that both tyrosines 1172 and 1222 are key elements in the binding sites for the SH2 domains of PTP2C. Tyrosine 39-48 insulin receptor substrate 1 Homo sapiens 115-120 7588273-8 1995 Furthermore, we found that mutation of tyrosines 1172 and 1222 totally prevents the insulin-induced association of IRS-1 with the SH2 domains of PTP2C, demonstrating that both tyrosines 1172 and 1222 are key elements in the binding sites for the SH2 domains of PTP2C. Tyrosine 176-185 insulin receptor substrate 1 Homo sapiens 115-120 8536716-1 1995 The adaptor molecule growth-factor-receptor-bound protein-2 (Grb2) plays a role in insulin action since it links tyrosine phosphorylated IRS-1 and Shc to the guanine-nucleotide-exchange factor, Sos, which initiates the mitogen-activated-protein (MAP) kinase cascade by producing Ras-GTP. Tyrosine 113-121 insulin receptor substrate 1 Homo sapiens 137-142 8550573-2 1996 IFN alpha also induces tyrosine phosphorylation of IRS-1, the principle substrate of the insulin receptor. Tyrosine 23-31 insulin receptor substrate 1 Homo sapiens 51-56 7559478-17 1995 Specifically, mutation of Leu-952 or Tyr-953 (at positions -7 and -8 from Tyr-960) markedly reduced IRS-1 interaction but had no effect upon SHC interaction. Tyrosine 37-40 insulin receptor substrate 1 Homo sapiens 100-105 7559478-17 1995 Specifically, mutation of Leu-952 or Tyr-953 (at positions -7 and -8 from Tyr-960) markedly reduced IRS-1 interaction but had no effect upon SHC interaction. Tyrosine 74-77 insulin receptor substrate 1 Homo sapiens 100-105 7559478-1 1995 Insulin receptor substrate 1 (IRS-1) and src homology and collagen protein (SHC) are signaling proteins which are rapidly phosphorylated on tyrosines after insulin receptor (IR) activation. Tyrosine 140-149 insulin receptor substrate 1 Homo sapiens 30-35 7559478-15 1995 We confirm that Tyr-960 within the NPEY motif of the IR is essential for both IRS-1 and SHC interaction and that Asn-957 and Pro-958 are essential for IRS-1 interaction and important but not critical for SHC interaction. Tyrosine 16-19 insulin receptor substrate 1 Homo sapiens 78-83 8690166-3 1995 Insulin-induced tyrosine phosphorylation of the major insulin receptor substrate IRS 1 was reduced by 50 +/- 7%, while its expression was decreased by 70 +/- 4%. Tyrosine 16-24 insulin receptor substrate 1 Homo sapiens 81-86 7646434-0 1995 Ethanol inhibits insulin receptor substrate-1 tyrosine phosphorylation and insulin-stimulated neuronal thread protein gene expression. Tyrosine 46-54 insulin receptor substrate 1 Homo sapiens 17-45 7646434-6 1995 The effects of ethanol on NTP gene expression were associated with impaired insulin-mediated tyrosine phosphorylation of both the insulin receptor beta subunit and the insulin receptor substrate-1 (IRS-1), resulting in decreased association of phosphatidylinositol 3-kinase with IRS-1. Tyrosine 93-101 insulin receptor substrate 1 Homo sapiens 168-196 7646434-6 1995 The effects of ethanol on NTP gene expression were associated with impaired insulin-mediated tyrosine phosphorylation of both the insulin receptor beta subunit and the insulin receptor substrate-1 (IRS-1), resulting in decreased association of phosphatidylinositol 3-kinase with IRS-1. Tyrosine 93-101 insulin receptor substrate 1 Homo sapiens 198-203 7537758-5 1995 In the lean subjects, tyrosine phosphorylation of the insulin receptor and insulin receptor substrate-1 (IRS-1), measured by immunoblotting with anti-phosphotyrosine antibodies, was significantly increased by insulin at all time points. Tyrosine 22-30 insulin receptor substrate 1 Homo sapiens 105-110 7549895-3 1995 Activation of these receptors also leads to pronounced and rapid tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) in cells of connective tissue origin. Tyrosine 65-73 insulin receptor substrate 1 Homo sapiens 93-121 7549895-3 1995 Activation of these receptors also leads to pronounced and rapid tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) in cells of connective tissue origin. Tyrosine 65-73 insulin receptor substrate 1 Homo sapiens 123-128 7549895-5 1995 IRS-1 and 4PS possess a number of tyrosine phosphorylation sites that are within motifs that bind specific SH2-containing molecules known to be involved in mitogenic signaling such as PI-3 kinase, SHPTP-2 (Syp) and Grb-2. Tyrosine 34-42 insulin receptor substrate 1 Homo sapiens 0-13 7541045-1 1995 Insulin receptor substrate-1 (IRS-1) and SHC become rapidly phosphorylated upon tyrosines after insulin-like growth factor I receptor (IGFIR) activation. Tyrosine 80-89 insulin receptor substrate 1 Homo sapiens 0-28 7541045-1 1995 Insulin receptor substrate-1 (IRS-1) and SHC become rapidly phosphorylated upon tyrosines after insulin-like growth factor I receptor (IGFIR) activation. Tyrosine 80-89 insulin receptor substrate 1 Homo sapiens 30-35 7541045-7 1995 We conclude that SHC and IRS-1 interact with the tyrosine-phosphorylated NPEY motif of the IGFIR, and that both proteins interact via related motifs located in their amino termini. Tyrosine 49-57 insulin receptor substrate 1 Homo sapiens 25-30 7543144-2 1995 After phosphorylation of tyrosine residues within the YMXM or YXXM motifs, IRS-1 associates with phosphatidylinositol-3 kinase (PI3K). Tyrosine 25-33 insulin receptor substrate 1 Homo sapiens 75-80 7608146-1 1995 Interferon-alpha (IFN alpha) induces rapid tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1), a docking protein with multiple tyrosine phosphorylation sites that bind to the Src homology 2 (SH2) domains of various signaling proteins. Tyrosine 43-51 insulin receptor substrate 1 Homo sapiens 75-103 7608146-1 1995 Interferon-alpha (IFN alpha) induces rapid tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1), a docking protein with multiple tyrosine phosphorylation sites that bind to the Src homology 2 (SH2) domains of various signaling proteins. Tyrosine 43-51 insulin receptor substrate 1 Homo sapiens 105-110 7608146-1 1995 Interferon-alpha (IFN alpha) induces rapid tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1), a docking protein with multiple tyrosine phosphorylation sites that bind to the Src homology 2 (SH2) domains of various signaling proteins. Tyrosine 145-153 insulin receptor substrate 1 Homo sapiens 75-103 7608146-1 1995 Interferon-alpha (IFN alpha) induces rapid tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1), a docking protein with multiple tyrosine phosphorylation sites that bind to the Src homology 2 (SH2) domains of various signaling proteins. Tyrosine 145-153 insulin receptor substrate 1 Homo sapiens 105-110 7608146-2 1995 During IFN alpha stimulation, the p85 regulatory subunit of the phosphatidylinositol 3"-kinase binds via its SH2 domains to tyrosine-phosphorylated IRS-1, and phosphatidylinositol 3"-kinase activity is detected in association with IRS-1. Tyrosine 124-132 insulin receptor substrate 1 Homo sapiens 148-153 7608146-2 1995 During IFN alpha stimulation, the p85 regulatory subunit of the phosphatidylinositol 3"-kinase binds via its SH2 domains to tyrosine-phosphorylated IRS-1, and phosphatidylinositol 3"-kinase activity is detected in association with IRS-1. Tyrosine 124-132 insulin receptor substrate 1 Homo sapiens 231-236 7619042-6 1995 Insulin, but not dinitrophenol, caused tyrosine phosphorylation of several polypeptides, including the insulin-receptor substrate-1 and mitogen-activated protein kinase. Tyrosine 39-47 insulin receptor substrate 1 Homo sapiens 103-131 7782332-6 1995 The ability of GH receptor (GHR) to transduce the signal for IRS-1 tyrosyl phosphorylation is mediated by the intracellular region of GHR between amino acids 295 and 380 by a mechanism not involving the two tyrosines in this region. Tyrosine 207-216 insulin receptor substrate 1 Homo sapiens 61-66 7539611-11 1995 Binding of p60 to p85 is similar to the interaction between p85 and IRS-1 in that a tyrosine-phosphorylated peptide containing the YVXM motif can inhibit the association. Tyrosine 84-92 insulin receptor substrate 1 Homo sapiens 68-73 7542850-2 1995 Growth factor receptor kinases, such as IN and EGF, phosphorylate insulin receptor substrate (IRS-1) and p36 protein kinase substrate, respectively, on tyrosine residues. Tyrosine 152-160 insulin receptor substrate 1 Homo sapiens 94-99 7537852-7 1995 These observations suggest that paxillin serves as an adapter protein, similar to insulin receptor substrate 1, and that pp125FAK may regulate the formation of signaling complexes by directing the phosphorylation of paxillin on tyrosine. Tyrosine 228-236 insulin receptor substrate 1 Homo sapiens 82-110 7818531-1 1995 Insulin receptor tyrosine kinase activity accounts for tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1), but the serine kinase(s) responsible for serine phosphorylation of IRS-1 is(are) unknown. Tyrosine 17-25 insulin receptor substrate 1 Homo sapiens 83-111 7806540-3 1994 Insulin receptors induce p21ras-GTP formation by two possible mechanisms: tyrosine phosphorylation of insulin receptor substrate 1 (IRS1) and its subsequent association with Grb2, or Shc phosphorylation and its subsequent association with Grb2. Tyrosine 74-82 insulin receptor substrate 1 Homo sapiens 102-130 7806540-3 1994 Insulin receptors induce p21ras-GTP formation by two possible mechanisms: tyrosine phosphorylation of insulin receptor substrate 1 (IRS1) and its subsequent association with Grb2, or Shc phosphorylation and its subsequent association with Grb2. Tyrosine 74-82 insulin receptor substrate 1 Homo sapiens 132-136 7806540-6 1994 In cell lines expressing wild type or mutant Y1158F,Y1162,Y1163 (FYY) receptors, insulin stimulated tyrosine phosphorylation of IRS1 and Shc and the formation of IRS1.Grb2 and Shc.Grb2 protein complexes, together with an increase in p21ras-GTP. Tyrosine 100-108 insulin receptor substrate 1 Homo sapiens 128-132 7806540-7 1994 Cell lines expressing mutant Y1158,Y1162F,Y1163F (YFF) receptors showed insulin-induced tyrosine phosphorylation of Shc, Shc.Grb2 complex formation, and p21ras-GTP formation, whereas tyrosine phosphorylation of IRS1 was strongly decreased and formation of IRS1.Grb2 complexes was undetectable. Tyrosine 88-96 insulin receptor substrate 1 Homo sapiens 211-215 7806540-7 1994 Cell lines expressing mutant Y1158,Y1162F,Y1163F (YFF) receptors showed insulin-induced tyrosine phosphorylation of Shc, Shc.Grb2 complex formation, and p21ras-GTP formation, whereas tyrosine phosphorylation of IRS1 was strongly decreased and formation of IRS1.Grb2 complexes was undetectable. Tyrosine 88-96 insulin receptor substrate 1 Homo sapiens 256-260 7983051-1 1994 Expression of the insulin receptor substrate-1 (IRS1) or Shc cDNA resulted in both increased protein and insulin-stimulated tyrosine phosphorylation of IRS1 and Shc proteins, respectively. Tyrosine 124-132 insulin receptor substrate 1 Homo sapiens 18-46 7983051-1 1994 Expression of the insulin receptor substrate-1 (IRS1) or Shc cDNA resulted in both increased protein and insulin-stimulated tyrosine phosphorylation of IRS1 and Shc proteins, respectively. Tyrosine 124-132 insulin receptor substrate 1 Homo sapiens 48-52 7983051-1 1994 Expression of the insulin receptor substrate-1 (IRS1) or Shc cDNA resulted in both increased protein and insulin-stimulated tyrosine phosphorylation of IRS1 and Shc proteins, respectively. Tyrosine 124-132 insulin receptor substrate 1 Homo sapiens 152-156 7864629-3 1995 A peptide containing acidic residues N-terminal to the substrate Tyr as well as the Tyr-Met-Xaa-Met motif of the insulin receptor substrate 1 had a Km value of 15 microM, the lowest value for a synthetic peptide reported to date. Tyrosine 84-87 insulin receptor substrate 1 Homo sapiens 113-141 7818531-1 1995 Insulin receptor tyrosine kinase activity accounts for tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1), but the serine kinase(s) responsible for serine phosphorylation of IRS-1 is(are) unknown. Tyrosine 17-25 insulin receptor substrate 1 Homo sapiens 113-118 7818531-5 1995 In complexes of tyrosine phosphorylated recombinant IRS-1 and PI3-kinase, phosphorylation of IRS-1 was associated with decreased phosphorylation of the p85 subunit of PI3-kinase. Tyrosine 16-24 insulin receptor substrate 1 Homo sapiens 52-57 7818531-5 1995 In complexes of tyrosine phosphorylated recombinant IRS-1 and PI3-kinase, phosphorylation of IRS-1 was associated with decreased phosphorylation of the p85 subunit of PI3-kinase. Tyrosine 16-24 insulin receptor substrate 1 Homo sapiens 93-98 7998930-1 1994 Insulin receptor substrate (IRS) 1, which is tyrosine phosphorylated in response to insulin, presents multiple serine/threonine phosphorylation sites. Tyrosine 45-53 insulin receptor substrate 1 Homo sapiens 0-34 7893993-9 1994 In contrast, the insulin receptor does not bind Grb2 directly but rather induces the tyrosine phosphorylation of two proteins, insulin receptor substrate-1 and Shc, that bind the Grb2/Sos complex. Tyrosine 85-93 insulin receptor substrate 1 Homo sapiens 127-155 8119950-3 1994 Simultaneously, in okadaic acid-treated 3T3-L1 adipocytes, the reduced IRS 1 tyrosine phosphorylation was linked to a decrease in its electrophoretic mobility due to phosphorylation on serine/threonine residues. Tyrosine 77-85 insulin receptor substrate 1 Homo sapiens 71-76 7929151-6 1994 These results suggest that the ErbB3 protein can be phosphorylated on tyrosine residues by a cross-phosphorylation mechanism and that the phosphorylated ErbB3 protein can couple other growth factor receptor protein tyrosine kinases to the PI 3-kinase pathway in a manner similar to the insulin receptor substrate 1 protein. Tyrosine 70-78 insulin receptor substrate 1 Homo sapiens 286-314 7520748-2 1994 IRS-1 contains nine potential tyrosine phosphorylation sites within YMXM or YXXM sequences known to bind to the two SH2 domains on the 85-kDa regulatory subunit of PtdIns 3"-kinase. Tyrosine 30-38 insulin receptor substrate 1 Homo sapiens 0-5 7520748-4 1994 We demonstrated for the first time that IRS-1-derived peptides containing two tyrosine phosphorylated YMXM motifs are capable of stimulating PtdIns 3"-kinase activity in the cytosol of 3T3-L1 adipocytes at nanomolar concentrations, similar to that required by purified phosphoryl-IRS-1 [Lamphere, M., Carpenter, C. L., Sheng, Z., Kallen, R. G., & Lienhard, G. E. (1994) Am. Tyrosine 78-86 insulin receptor substrate 1 Homo sapiens 40-45 7520748-4 1994 We demonstrated for the first time that IRS-1-derived peptides containing two tyrosine phosphorylated YMXM motifs are capable of stimulating PtdIns 3"-kinase activity in the cytosol of 3T3-L1 adipocytes at nanomolar concentrations, similar to that required by purified phosphoryl-IRS-1 [Lamphere, M., Carpenter, C. L., Sheng, Z., Kallen, R. G., & Lienhard, G. E. (1994) Am. Tyrosine 78-86 insulin receptor substrate 1 Homo sapiens 280-285 8048169-2 1994 IRS-1 undergoes multisite tyrosine phosphorylation and mediates downstream signals by "docking" various proteins that contain Src homology 2 domains. Tyrosine 26-34 insulin receptor substrate 1 Homo sapiens 0-5 7515062-1 1994 The phosphotyrosine (Tyr(P)) form of insulin receptor substrate 1 (IRS-1) is a key component in insulin signaling. Tyrosine 21-24 insulin receptor substrate 1 Homo sapiens 37-65 7515062-1 1994 The phosphotyrosine (Tyr(P)) form of insulin receptor substrate 1 (IRS-1) is a key component in insulin signaling. Tyrosine 21-24 insulin receptor substrate 1 Homo sapiens 67-72 7515062-2 1994 Our previous study revealed that Tyr(P) IRS-1 binds to the widely distributed tyrosine phosphatase PTP2C through the src homology 2 (SH2) domains of the latter. Tyrosine 33-36 insulin receptor substrate 1 Homo sapiens 40-45 7515062-4 1994 Tyr(P) IRS-1 was prepared by phosphorylation of recombinant IRS-1 with recombinant cytoplasmic insulin receptor kinase (CIRK). Tyrosine 0-3 insulin receptor substrate 1 Homo sapiens 7-12 7515062-4 1994 Tyr(P) IRS-1 was prepared by phosphorylation of recombinant IRS-1 with recombinant cytoplasmic insulin receptor kinase (CIRK). Tyrosine 0-3 insulin receptor substrate 1 Homo sapiens 60-65 7515062-5 1994 PTP2C rapidly dephosphorylated Tyr(P) IRS-1; dephosphorylation by delta PTP2C was approximately one-third as fast. Tyrosine 31-34 insulin receptor substrate 1 Homo sapiens 38-43 7515062-7 1994 These results indicate that the binding of Tyr(P) residues on IRS-1 to the SH2 domain(s) of PTP2C enhances its activity toward IRS-1 and suggest that PTP2C is the phosphatase responsible for the dephosphorylation of IRS-1 in vivo. Tyrosine 43-46 insulin receptor substrate 1 Homo sapiens 62-67 7515062-7 1994 These results indicate that the binding of Tyr(P) residues on IRS-1 to the SH2 domain(s) of PTP2C enhances its activity toward IRS-1 and suggest that PTP2C is the phosphatase responsible for the dephosphorylation of IRS-1 in vivo. Tyrosine 43-46 insulin receptor substrate 1 Homo sapiens 127-132 7515062-7 1994 These results indicate that the binding of Tyr(P) residues on IRS-1 to the SH2 domain(s) of PTP2C enhances its activity toward IRS-1 and suggest that PTP2C is the phosphatase responsible for the dephosphorylation of IRS-1 in vivo. Tyrosine 43-46 insulin receptor substrate 1 Homo sapiens 127-132 7513703-1 1994 The cytoplasmic insulin receptor substrate-1 (IRS-1), which is multiply phosphorylated in vivo on tyrosine residues, is a known binding protein for the tandem src homology 2 (SH2) domain-containing protein tyrosine phosphatase, SH-PTP2. Tyrosine 98-106 insulin receptor substrate 1 Homo sapiens 16-44 7513703-1 1994 The cytoplasmic insulin receptor substrate-1 (IRS-1), which is multiply phosphorylated in vivo on tyrosine residues, is a known binding protein for the tandem src homology 2 (SH2) domain-containing protein tyrosine phosphatase, SH-PTP2. Tyrosine 98-106 insulin receptor substrate 1 Homo sapiens 46-51 14731733-2 1994 Tyrosine-phosphorylated IRS1 then serves as a docking/effector protein for at least four Src homology 2 (SH2)-domain proteins involved in signal transduction. Tyrosine 0-8 insulin receptor substrate 1 Homo sapiens 24-28 8144662-1 1994 Insulin stimulates tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and She in Rat1 fibroblasts overexpressing wild type insulin receptors. Tyrosine 19-27 insulin receptor substrate 1 Homo sapiens 47-75 8144662-1 1994 Insulin stimulates tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and She in Rat1 fibroblasts overexpressing wild type insulin receptors. Tyrosine 19-27 insulin receptor substrate 1 Homo sapiens 77-82 8144662-3 1994 The time course of insulin-stimulated tyrosine phosphorylation of IRS-1 was rapid, whereas Shc phosphorylation was relatively slow. Tyrosine 38-46 insulin receptor substrate 1 Homo sapiens 66-71 8144662-5 1994 Thus, the kinetics of Grb2 association with IRS-1 and She corresponded closely to the time course of tyrosine phosphorylation of IRS-1 and Shc, respectively. Tyrosine 101-109 insulin receptor substrate 1 Homo sapiens 44-49 8144662-5 1994 Thus, the kinetics of Grb2 association with IRS-1 and She corresponded closely to the time course of tyrosine phosphorylation of IRS-1 and Shc, respectively. Tyrosine 101-109 insulin receptor substrate 1 Homo sapiens 129-134 7504175-1 1993 IRS-1 (insulin receptor substrate 1) is a principal insulin receptor substrate that undergoes tyrosine phosphorylation during insulin stimulation. Tyrosine 94-102 insulin receptor substrate 1 Homo sapiens 0-5 8265614-4 1993 The interaction between IRS-1 and Nck is mediated by the binding of the SH2 domain of Nck to tyrosine-phosphorylated IRS-1. Tyrosine 93-101 insulin receptor substrate 1 Homo sapiens 24-29 8265614-4 1993 The interaction between IRS-1 and Nck is mediated by the binding of the SH2 domain of Nck to tyrosine-phosphorylated IRS-1. Tyrosine 93-101 insulin receptor substrate 1 Homo sapiens 117-122 7504175-3 1993 Tyrosine-phosphorylated IRS-1 binds specifically to various cellular proteins containing Src homology 2 (SH2) domains (SH2 proteins). Tyrosine 0-8 insulin receptor substrate 1 Homo sapiens 24-29 7504175-4 1993 We identified some of the tyrosine residues of IRS-1 that undergo insulin-stimulated phosphorylation by the purified insulin receptor and in intact cells during insulin stimulation. Tyrosine 26-34 insulin receptor substrate 1 Homo sapiens 47-52 8290602-1 1994 Insulin treatment of mammalian cells immediately stimulates the tyrosine phosphorylation of a cellular protein of 185 kDa referred to as pp185 or IRS-1 (insulin receptor substrate 1). Tyrosine 64-72 insulin receptor substrate 1 Homo sapiens 146-151 8290602-1 1994 Insulin treatment of mammalian cells immediately stimulates the tyrosine phosphorylation of a cellular protein of 185 kDa referred to as pp185 or IRS-1 (insulin receptor substrate 1). Tyrosine 64-72 insulin receptor substrate 1 Homo sapiens 153-181 7504175-1 1993 IRS-1 (insulin receptor substrate 1) is a principal insulin receptor substrate that undergoes tyrosine phosphorylation during insulin stimulation. Tyrosine 94-102 insulin receptor substrate 1 Homo sapiens 7-35 8282127-2 1993 Insulin promotes the formation of a complex between tyrosine-phosphorylated IRS-1 and several proteins including phosphoinositide(PI) 3-kinase, a heterodimer consisting of regulatory 85-kDa (p85) and catalytic 110-kDa (p110) subunits, GRB2 and Syp via the Src homology region 2 (SH2) domains. Tyrosine 52-60 insulin receptor substrate 1 Homo sapiens 76-81 8227078-1 1993 Several tyrosine phosphorylation sites in the insulin receptor kinase substrate IRS-1 are predicted to be within Tyr-Met-X-Met (YMXM) motifs, and synthetic peptides corresponding to these sequences are excellent substrates for the insulin receptor kinase in vitro (Shoelson, S. E., Chatterjee, S., Chaudhuri, M., and White, M. F. (1992) Proc. Tyrosine 8-16 insulin receptor substrate 1 Homo sapiens 80-85 8227078-1 1993 Several tyrosine phosphorylation sites in the insulin receptor kinase substrate IRS-1 are predicted to be within Tyr-Met-X-Met (YMXM) motifs, and synthetic peptides corresponding to these sequences are excellent substrates for the insulin receptor kinase in vitro (Shoelson, S. E., Chatterjee, S., Chaudhuri, M., and White, M. F. (1992) Proc. Tyrosine 113-116 insulin receptor substrate 1 Homo sapiens 80-85 7906861-8 1993 alpha 2HSG also inhibits both insulin-induced tyrosine phosphorylation of IRS-1 and the association of IRS-1 with the p85 subunit of phosphatidylinositol-3 kinase in H-35 hepatoma cells. Tyrosine 46-54 insulin receptor substrate 1 Homo sapiens 74-79 8396927-9 1993 These results suggest that the tyrosine phosphorylation of IRS-1 and activation of PI3-kinase may be involved in the signaling pathway of the insulin-stimulated GLUT4 translocation. Tyrosine 31-39 insulin receptor substrate 1 Homo sapiens 59-64 8393870-3 1993 In CHO-Y960F cells, tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1), the activation of phosphatidylinositol 3-kinase in the anti-phosphotyrosine and anti-IRS-1 immunoprecipitates, the activation of mitogen-activated protein (MAP) kinase, and biological actions were also impaired. Tyrosine 20-28 insulin receptor substrate 1 Homo sapiens 48-76 8393870-3 1993 In CHO-Y960F cells, tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1), the activation of phosphatidylinositol 3-kinase in the anti-phosphotyrosine and anti-IRS-1 immunoprecipitates, the activation of mitogen-activated protein (MAP) kinase, and biological actions were also impaired. Tyrosine 20-28 insulin receptor substrate 1 Homo sapiens 78-83 8393870-6 1993 These data suggest that: 1) Tyr960 is important for the recognition of pp185/IRS-1, the association of phosphatidylinositol 3-kinase with pp185/IRS-1, and the activation of MAP kinase; 2) MAP kinase may lie downstream of pp185/IRS-1 in insulin"s signal transduction; and 3) the juxtamembrane domain, but not NPXY or individual tyrosines, is important for insulin internalization. Tyrosine 327-336 insulin receptor substrate 1 Homo sapiens 77-82 8393870-6 1993 These data suggest that: 1) Tyr960 is important for the recognition of pp185/IRS-1, the association of phosphatidylinositol 3-kinase with pp185/IRS-1, and the activation of MAP kinase; 2) MAP kinase may lie downstream of pp185/IRS-1 in insulin"s signal transduction; and 3) the juxtamembrane domain, but not NPXY or individual tyrosines, is important for insulin internalization. Tyrosine 327-336 insulin receptor substrate 1 Homo sapiens 144-149 8393870-6 1993 These data suggest that: 1) Tyr960 is important for the recognition of pp185/IRS-1, the association of phosphatidylinositol 3-kinase with pp185/IRS-1, and the activation of MAP kinase; 2) MAP kinase may lie downstream of pp185/IRS-1 in insulin"s signal transduction; and 3) the juxtamembrane domain, but not NPXY or individual tyrosines, is important for insulin internalization. Tyrosine 327-336 insulin receptor substrate 1 Homo sapiens 144-149 8513971-5 1993 The 14 potential Tyr phosphorylation sites include 6 Tyr-Met-X-Met motifs and 3 Tyr-X-X-Met motifs that are completely conserved in human IRS-1. Tyrosine 17-20 insulin receptor substrate 1 Homo sapiens 138-143 8513971-10 1993 When human IRS-1 cDNA was expressed in Chinese hamster ovary cells, the protein migrated between 170,000-180,000 M(r) in sodium dodecyl sulfate-polyacrylamide gel electrophoresis and was rapidly Tyr phosphorylated upon insulin stimulation. Tyrosine 195-198 insulin receptor substrate 1 Homo sapiens 11-16 8505282-1 1993 The insulin receptor substrate 1 (IRS1) is a protein that is rapidly phosphorylated on tyrosine by the activated insulin receptor. Tyrosine 87-95 insulin receptor substrate 1 Homo sapiens 4-32 8316835-6 1993 In response to insulin stimulation, this complex bound to tyrosine-phosphorylated IRS-1 (insulin receptor substrate-1) and Shc. Tyrosine 58-66 insulin receptor substrate 1 Homo sapiens 82-87 8316835-6 1993 In response to insulin stimulation, this complex bound to tyrosine-phosphorylated IRS-1 (insulin receptor substrate-1) and Shc. Tyrosine 58-66 insulin receptor substrate 1 Homo sapiens 89-117 8505282-1 1993 The insulin receptor substrate 1 (IRS1) is a protein that is rapidly phosphorylated on tyrosine by the activated insulin receptor. Tyrosine 87-95 insulin receptor substrate 1 Homo sapiens 34-38 8505282-5 1993 The association of Syp with IRS1 apparently occurs between the SH2 domains of Syp and Tyr(P)-containing sequences of IRS1, since a fusion protein containing only the SH2 domains of Syp bound the Tyr(P) form of IRS1. Tyrosine 86-89 insulin receptor substrate 1 Homo sapiens 28-32 8505282-5 1993 The association of Syp with IRS1 apparently occurs between the SH2 domains of Syp and Tyr(P)-containing sequences of IRS1, since a fusion protein containing only the SH2 domains of Syp bound the Tyr(P) form of IRS1. Tyrosine 86-89 insulin receptor substrate 1 Homo sapiens 117-121 8505282-5 1993 The association of Syp with IRS1 apparently occurs between the SH2 domains of Syp and Tyr(P)-containing sequences of IRS1, since a fusion protein containing only the SH2 domains of Syp bound the Tyr(P) form of IRS1. Tyrosine 86-89 insulin receptor substrate 1 Homo sapiens 117-121 8505282-5 1993 The association of Syp with IRS1 apparently occurs between the SH2 domains of Syp and Tyr(P)-containing sequences of IRS1, since a fusion protein containing only the SH2 domains of Syp bound the Tyr(P) form of IRS1. Tyrosine 195-198 insulin receptor substrate 1 Homo sapiens 28-32 7685118-2 1993 In most mammalian cell types, this results in rapid tyrosine phosphorylation of a high-molecular-weight substrate termed insulin receptor substrate 1 (IRS-1). Tyrosine 52-60 insulin receptor substrate 1 Homo sapiens 121-149 8388384-13 1993 We also demonstrated that fusion protein of ASH was able to bind the fusion protein of tyrosine-phosphorylated IRS-1 fragments, suggesting that ASH is able to bind tyrosine-phosphorylated IRS-1 directly. Tyrosine 164-172 insulin receptor substrate 1 Homo sapiens 188-193 8491186-0 1993 The SH2/SH3 domain-containing protein GRB2 interacts with tyrosine-phosphorylated IRS1 and Shc: implications for insulin control of ras signalling. Tyrosine 58-66 insulin receptor substrate 1 Homo sapiens 82-86 8491186-8 1993 Interestingly, both GRB2 and phosphatidylinositol-3 (PI-3) kinase can simultaneously bind distinct tyrosine phosphorylated regions on the same IRS-1 molecule, suggesting a mechanism whereby IRS-1 could provide the core for a large signalling complex. Tyrosine 99-107 insulin receptor substrate 1 Homo sapiens 143-148 8491186-8 1993 Interestingly, both GRB2 and phosphatidylinositol-3 (PI-3) kinase can simultaneously bind distinct tyrosine phosphorylated regions on the same IRS-1 molecule, suggesting a mechanism whereby IRS-1 could provide the core for a large signalling complex. Tyrosine 99-107 insulin receptor substrate 1 Homo sapiens 190-195 1312712-1 1992 Of 34 tyrosine residues in insulin receptor substrate 1 (IRS-1), 14 are adjacent to acidic residues, suggesting that they might be phosphorylation sites. Tyrosine 6-14 insulin receptor substrate 1 Homo sapiens 27-55 7685118-2 1993 In most mammalian cell types, this results in rapid tyrosine phosphorylation of a high-molecular-weight substrate termed insulin receptor substrate 1 (IRS-1). Tyrosine 52-60 insulin receptor substrate 1 Homo sapiens 151-156 1332046-1 1992 IRS-1 is an insulin receptor substrate that undergoes tyrosine phosphorylation and associates with the phosphatidylinositol (PtdIns) 3"-kinase immediately after insulin stimulation. Tyrosine 54-62 insulin receptor substrate 1 Homo sapiens 0-5 1332046-2 1992 Recombinant IRS-1 protein was tyrosine phosphorylated by the insulin receptor in vitro and associated with the PtdIns 3"-kinase from lysates of quiescent 3T3 fibroblasts. Tyrosine 30-38 insulin receptor substrate 1 Homo sapiens 12-17 1332046-3 1992 Bacterial fusion proteins containing the src homology 2 domains (SH2 domains) of the 85-kDa subunit (p85) of the PtdIns 3"-kinase bound quantitatively to tyrosine phosphorylated, but not unphosphorylated, IRS-1, and this association was blocked by phosphotyrosine-containing synthetic peptides. Tyrosine 154-162 insulin receptor substrate 1 Homo sapiens 205-210 1332046-6 1992 These data suggest that the interaction between PtdIns 3"-kinase and IRS-1 is mediated by tyrosine phosphorylated motifs on IRS-1 and the SH2 domains of p85, and IRS-1 activates PtdIns 3"-kinase by binding to the SH2 domains of p85. Tyrosine 90-98 insulin receptor substrate 1 Homo sapiens 69-74 1332046-6 1992 These data suggest that the interaction between PtdIns 3"-kinase and IRS-1 is mediated by tyrosine phosphorylated motifs on IRS-1 and the SH2 domains of p85, and IRS-1 activates PtdIns 3"-kinase by binding to the SH2 domains of p85. Tyrosine 90-98 insulin receptor substrate 1 Homo sapiens 124-129 1332046-6 1992 These data suggest that the interaction between PtdIns 3"-kinase and IRS-1 is mediated by tyrosine phosphorylated motifs on IRS-1 and the SH2 domains of p85, and IRS-1 activates PtdIns 3"-kinase by binding to the SH2 domains of p85. Tyrosine 90-98 insulin receptor substrate 1 Homo sapiens 124-129 8388384-12 1993 Incubation of an ASH fusion protein with the lysates of insulin-stimulated CHO-HIR cells revealed that the fusion protein of ASH was able to bind the tyrosine-phosphorylated 170-kDa protein that was recognized by alpha IRS-1. Tyrosine 150-158 insulin receptor substrate 1 Homo sapiens 219-224 8388384-13 1993 We also demonstrated that fusion protein of ASH was able to bind the fusion protein of tyrosine-phosphorylated IRS-1 fragments, suggesting that ASH is able to bind tyrosine-phosphorylated IRS-1 directly. Tyrosine 87-95 insulin receptor substrate 1 Homo sapiens 111-116 8388384-13 1993 We also demonstrated that fusion protein of ASH was able to bind the fusion protein of tyrosine-phosphorylated IRS-1 fragments, suggesting that ASH is able to bind tyrosine-phosphorylated IRS-1 directly. Tyrosine 87-95 insulin receptor substrate 1 Homo sapiens 188-193 8388384-13 1993 We also demonstrated that fusion protein of ASH was able to bind the fusion protein of tyrosine-phosphorylated IRS-1 fragments, suggesting that ASH is able to bind tyrosine-phosphorylated IRS-1 directly. Tyrosine 164-172 insulin receptor substrate 1 Homo sapiens 111-116 8382493-1 1993 One of the first steps that follows insulin receptor activation is the tyrosine phosphorylation of the 160-185 kDa insulin receptor substrate IRS-1. Tyrosine 71-79 insulin receptor substrate 1 Homo sapiens 142-147 1334490-3 1992 Insulin also induced an association of p85 with the tyrosine-phosphorylated insulin receptor substrate 1 (IRS-1) and other phosphorylated proteins ranging in size from 100 to 170 kDa but not with the activated insulin receptor. Tyrosine 52-60 insulin receptor substrate 1 Homo sapiens 106-111 1334490-4 1992 In vitro reconstitution studies were used to show p85 in the active PI 3-kinase associated with the tyrosine-phosphorylated IRS-1 but not with the activated insulin receptor. Tyrosine 100-108 insulin receptor substrate 1 Homo sapiens 124-129 1334490-5 1992 Competition studies using synthetic phosphopeptides corresponding to potential tyrosine phosphorylation sites of IRS-1 revealed that phosphopeptides containing YMXM motifs inhibited this association with different potencies, whereas nonphosphorylated analogues and a phosphopeptide containing the EYYE motif had no effect. Tyrosine 79-87 insulin receptor substrate 1 Homo sapiens 113-118 1334490-6 1992 Src homology region 2 domains of p85 expressed as glutathione S-transferase fusion proteins also bound to tyrosine-phosphorylated IRS-1. Tyrosine 106-114 insulin receptor substrate 1 Homo sapiens 130-135 1380456-2 1992 IRS-1 contains nine tyrosine phosphorylation sites in YXXM (Tyr-Xxx-Xxx-Met) motifs. Tyrosine 20-28 insulin receptor substrate 1 Homo sapiens 0-5 1380456-2 1992 IRS-1 contains nine tyrosine phosphorylation sites in YXXM (Tyr-Xxx-Xxx-Met) motifs. Tyrosine 60-63 insulin receptor substrate 1 Homo sapiens 0-5 1312712-1 1992 Of 34 tyrosine residues in insulin receptor substrate 1 (IRS-1), 14 are adjacent to acidic residues, suggesting that they might be phosphorylation sites. Tyrosine 6-14 insulin receptor substrate 1 Homo sapiens 57-62 35074429-5 2022 Inhibition of P300 acetyltransferase activity by C646 drastically increased tyrosine phosphorylation of the insulin receptor protein substrates (IRS1/2) without affecting the tyrosine phosphorylation of the beta subunit of the insulin receptor (IRbeta) in hepatocytes in the absence of insulin. Tyrosine 76-84 insulin receptor substrate 1 Homo sapiens 145-151 35625712-9 2022 According to our data, m- or o-Tyr incorporation into IRS-1 modifies its protein-protein interactions with regulating enzymes and effectors, thus IRS-1 eventually loses its capacity to play its role in insulin signaling, leading to insulin resistance. Tyrosine 31-34 insulin receptor substrate 1 Homo sapiens 54-59 35625712-9 2022 According to our data, m- or o-Tyr incorporation into IRS-1 modifies its protein-protein interactions with regulating enzymes and effectors, thus IRS-1 eventually loses its capacity to play its role in insulin signaling, leading to insulin resistance. Tyrosine 31-34 insulin receptor substrate 1 Homo sapiens 146-151 35460012-7 2022 It attenuates the ERK1/2-induced serine phosphorylation of IRS-1 and thus enhances IRS-1 tyrosine phosphorylation and Akt activation. Tyrosine 89-97 insulin receptor substrate 1 Homo sapiens 59-64 35460012-7 2022 It attenuates the ERK1/2-induced serine phosphorylation of IRS-1 and thus enhances IRS-1 tyrosine phosphorylation and Akt activation. Tyrosine 89-97 insulin receptor substrate 1 Homo sapiens 83-88 35166127-6 2022 RESULTS: D-allulose effectively controlled glycemic markers such as insulin and HbA1C, showing anti-diabetic effects by inhibiting the disruption of insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation and glucose transporter 4 (GLUT4) expression, in which the PI3K/Akt pathway is involved. Tyrosine 186-194 insulin receptor substrate 1 Homo sapiens 149-177 35166127-6 2022 RESULTS: D-allulose effectively controlled glycemic markers such as insulin and HbA1C, showing anti-diabetic effects by inhibiting the disruption of insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation and glucose transporter 4 (GLUT4) expression, in which the PI3K/Akt pathway is involved. Tyrosine 186-194 insulin receptor substrate 1 Homo sapiens 179-184 1311924-6 1992 180 kDa hIRS-1 protein was immunoprecipitated and found to be phosphorylated on tyrosine residue(s) following insulin stimulation of HuH-7 HCC cells. Tyrosine 80-88 insulin receptor substrate 1 Homo sapiens 8-14 1648180-6 1991 IRS-1 contains over ten potential tyrosine phosphorylation sites, six of which are in Tyr-Met-X-Met motifs. Tyrosine 34-42 insulin receptor substrate 1 Homo sapiens 0-5 1648180-6 1991 IRS-1 contains over ten potential tyrosine phosphorylation sites, six of which are in Tyr-Met-X-Met motifs. Tyrosine 86-89 insulin receptor substrate 1 Homo sapiens 0-5 1648180-7 1991 During insulin stimulation, the IRS-1 protein undergoes tyrosine phosphorylation and binds phosphatidylinositol 3-kinase, suggesting that IRS-1 acts as a multisite "docking" protein to bind signal-transducing molecules containing Src-homology 2 and Src-homology-3 domains. Tyrosine 56-64 insulin receptor substrate 1 Homo sapiens 32-37 1648180-7 1991 During insulin stimulation, the IRS-1 protein undergoes tyrosine phosphorylation and binds phosphatidylinositol 3-kinase, suggesting that IRS-1 acts as a multisite "docking" protein to bind signal-transducing molecules containing Src-homology 2 and Src-homology-3 domains. Tyrosine 56-64 insulin receptor substrate 1 Homo sapiens 138-143 35625712-8 2022 We found that phosphorylation of m- or o-Tyr containing IRS-1 segments by insulin receptor (IR) kinase was greatly reduced, PTP-1B phosphatase was incapable of dephosphorylating phosphorylated m- or o-Tyr IRS-1 peptides, and the SH2 domains of phosphoinositide 3-kinase (PI3K) bound the o-Tyr IRS-1 peptides with greatly reduced affinity. Tyrosine 41-44 insulin receptor substrate 1 Homo sapiens 56-61 35074429-8 2022 Intriguingly, we demonstrate that C646 activates IRbeta"s tyrosine kinase activity and directly promotes IRbeta interaction with IRS1/2, leading to the tyrosine phosphorylation of IRS1/2 and subsequent activation of insulin signaling even in the absence of insulin. Tyrosine 152-160 insulin receptor substrate 1 Homo sapiens 129-135 35074429-8 2022 Intriguingly, we demonstrate that C646 activates IRbeta"s tyrosine kinase activity and directly promotes IRbeta interaction with IRS1/2, leading to the tyrosine phosphorylation of IRS1/2 and subsequent activation of insulin signaling even in the absence of insulin. Tyrosine 152-160 insulin receptor substrate 1 Homo sapiens 180-186