PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 9139682-2 1997 In rat aortic vascular smooth muscle cells, IGF I (20 ng/ml) induced a sustained (>30 min) increase in the tyrosine phosphorylation of both Src-homology 2 domain-docking insulin receptor substrate 1 (IRS-1) and Src-homology 2-binding tyrosine phosphatase 1D (PTP-1D). Tyrosine 110-118 insulin receptor substrate 1 Rattus norvegicus 173-201 9139682-2 1997 In rat aortic vascular smooth muscle cells, IGF I (20 ng/ml) induced a sustained (>30 min) increase in the tyrosine phosphorylation of both Src-homology 2 domain-docking insulin receptor substrate 1 (IRS-1) and Src-homology 2-binding tyrosine phosphatase 1D (PTP-1D). Tyrosine 110-118 insulin receptor substrate 1 Rattus norvegicus 203-208 9139682-4 1997 Ang II (10(-7) M) also increased the tyrosine phosphorylation of IRS-1 (4-fold), PTP-1D (5-fold), and PTP-1D activity (3-4-fold), but with a more transient time course. Tyrosine 37-45 insulin receptor substrate 1 Rattus norvegicus 65-70 9139682-8 1997 Our findings show that the tyrosine phosphorylation of IRS-1 and PTP-1D represents a convergent intracellular signaling cascade stimulated by both growth factor (i.e. IGF I) and G-protein-coupled (i.e. AT1) receptors. Tyrosine 27-35 insulin receptor substrate 1 Rattus norvegicus 55-60 9222420-4 1996 We show that IRS-1 is present in rat aorta, and is tyrosine phosphorylated after insulin stimulation. Tyrosine 51-59 insulin receptor substrate 1 Rattus norvegicus 13-18 9139749-2 1997 Indeed, stimulation with insulin or insulin-like growth factor I led to the rapid tyrosine phosphorylation of both IRS-1 and IRS-2, which in turn activated phosphatidylinositol (PI) 3-kinase in L6 cells and rat skeletal muscle. Tyrosine 82-90 insulin receptor substrate 1 Rattus norvegicus 115-120 9139749-4 1997 The time courses of the PI 3-kinase activity associated with IRS-1 and IRS-2 paralleled the tyrosine phosphorylation of these proteins. Tyrosine 92-100 insulin receptor substrate 1 Rattus norvegicus 61-66 9065454-11 1997 Furthermore, p50alpha exhibits a markedly higher capacity for activation of associated PI 3-kinase via insulin stimulation and has a higher affinity for tyrosine-phosphorylated IRS-1 than the other isoforms. Tyrosine 153-161 insulin receptor substrate 1 Rattus norvegicus 177-182 8943955-4 1996 In this study, we observed that > or = 1 nmol/L insulin stimulated tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and activated IRS-1-dependent phosphatidylinositol 3"-kinase (PI 3"-kinase) and p70 S6 kinase (p70S6K) but not MAP kinase (extracellular signal-regulated kinase 2) and p90 S6 kinase (p90RSK). Tyrosine 70-78 insulin receptor substrate 1 Rattus norvegicus 128-133 9023010-4 1996 In addition, insulin-stimulated tyrosine phosphorylation of the endogenous insulin receptor substrates IRS-1 and Shc were decreased to 57% and 73% of control, respectively, and IRS-1 associated phosphatidylinositol 3"-kinase activity was reduced to 47% of control of the cells overexpressing LAR. Tyrosine 32-40 insulin receptor substrate 1 Rattus norvegicus 103-108 8703019-6 1996 In two animal models of insulin resistance the regulation of JAK2 tyrosine phosphorylation after insulin infusion paralleled the phosphorylation of the insulin receptor and of IRS-1. Tyrosine 66-74 insulin receptor substrate 1 Rattus norvegicus 176-181 8901609-2 1996 Following injection of AII into rats, we find that there is also a rapid tyrosine phosphorylation of the major insulin receptor substrates 1 and 2 (IRS-1 and IRS-2) in the heart. Tyrosine 73-81 insulin receptor substrate 1 Rattus norvegicus 111-146 8901609-2 1996 Following injection of AII into rats, we find that there is also a rapid tyrosine phosphorylation of the major insulin receptor substrates 1 and 2 (IRS-1 and IRS-2) in the heart. Tyrosine 73-81 insulin receptor substrate 1 Rattus norvegicus 148-153 7537739-6 1995 Insulin receptor substrate-1 tyrosine phosphorylation followed the kinetics of IRK activation in ENs not PM and a hypoglycemic response similar to that achieved with a pharmacological dose of insulin ensued. Tyrosine 29-37 insulin receptor substrate 1 Rattus norvegicus 0-28 8770909-6 1996 Although basal tyrosine phosphorylation of IRS-1 and SHC was evident, GH did not stimulate tyrosine phosphorylation of either of these proteins in liver or skeletal muscle. Tyrosine 15-23 insulin receptor substrate 1 Rattus norvegicus 43-48 8626623-0 1996 Sphingomyelinase and ceramide suppress insulin-induced tyrosine phosphorylation of the insulin receptor substrate-1. Tyrosine 55-63 insulin receptor substrate 1 Rattus norvegicus 87-115 8626623-2 1996 TNF was recently shown to interfere with insulin-induced tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1). Tyrosine 57-65 insulin receptor substrate 1 Rattus norvegicus 89-117 8626623-2 1996 TNF was recently shown to interfere with insulin-induced tyrosine phosphorylation of the insulin receptor substrate-1 (IRS-1). Tyrosine 57-65 insulin receptor substrate 1 Rattus norvegicus 119-124 8626623-3 1996 In this work we examined the possible effect of direct activation of the sphingomyelin pathway on insulin-induced tyrosine phosphorylation of IRS-1. Tyrosine 114-122 insulin receptor substrate 1 Rattus norvegicus 142-147 8626623-8 1996 A similar impact on IRS-1 tyrosine phosphorylation was observed after addition of cell-permeable ceramide analogs (C2 and C6). Tyrosine 26-34 insulin receptor substrate 1 Rattus norvegicus 20-25 8626623-9 1996 Comparable changes in IRS-1 tyrosine phosphorylation and electrophoretic mobility were found after exposure of cells to either TNF, SMase, or ceramide. Tyrosine 28-36 insulin receptor substrate 1 Rattus norvegicus 22-27 8626623-10 1996 Our findings suggest that TNF may utilize the sphingomyelin pathway in its effect on the insulin-stimulated tyrosine phosphorylation of IRS-1. Tyrosine 108-116 insulin receptor substrate 1 Rattus norvegicus 136-141 8579617-0 1996 G-protein and tyrosine kinase receptor cross-talk in rat aortic smooth muscle cells: thrombin- and angiotensin II-induced tyrosine phosphorylation of insulin receptor substrate-1 and insulin-like growth factor 1 receptor. Tyrosine 14-22 insulin receptor substrate 1 Rattus norvegicus 150-178 8579617-3 1996 In rat aortic smooth muscle cells we observed that both angiotensin II and thrombin induced rapid tyrosine phosphorylation of insulin receptor substrate-1. Tyrosine 98-106 insulin receptor substrate 1 Rattus norvegicus 126-154 7575404-0 1995 Angiotensin II induces tyrosine phosphorylation of insulin receptor substrate 1 and its association with phosphatidylinositol 3-kinase in rat heart. Tyrosine 23-31 insulin receptor substrate 1 Rattus norvegicus 51-79 7575404-7 1995 When the animals were pretreated for 1 h with DuP 753, a non-peptide AII-receptor 1 (AT1 receptor) antagonist, there was a marked reduction in the AII-induced tyrosine phosphorylation of IRS-1, suggesting that phosphorylation is initially mediated by the AT1 receptor. Tyrosine 159-167 insulin receptor substrate 1 Rattus norvegicus 187-192 7575404-8 1995 We conclude that AII stimulates tyrosine phosphorylation of IRS-1 and its association with PI 3-kinase. Tyrosine 32-40 insulin receptor substrate 1 Rattus norvegicus 60-65 7791763-3 1995 Significantly, all the insulin-induced tyrosine phosphorylation sites identified in rat IRS-1, including those responsible for binding to the Src homology domains of phosphatidylinositol (PI) 3-kinase, Syp and Grb2, are conserved in XIRS-L. Tyrosine 39-47 insulin receptor substrate 1 Rattus norvegicus 88-93 7738028-7 1995 The normal heterotetrameric receptors possess kinase activity in vivo leading to tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and its association with the p85 regulatory subunit of phosphatidyl inositol 3-kinase. Tyrosine 81-89 insulin receptor substrate 1 Rattus norvegicus 109-137 7738028-7 1995 The normal heterotetrameric receptors possess kinase activity in vivo leading to tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and its association with the p85 regulatory subunit of phosphatidyl inositol 3-kinase. Tyrosine 81-89 insulin receptor substrate 1 Rattus norvegicus 139-144 8670300-2 1996 Increased tyrosine phosphorylation levels of insulin receptors (IRs) and insulin receptor substrate 1 (IRS-1) in response to insulin were not observed in fatty rats. Tyrosine 10-18 insulin receptor substrate 1 Rattus norvegicus 103-108 8670300-5 1996 In contrast, insulin-stimulated tyrosine phosphorylation of IR and IRS-1 and PI 3-kinase activity in lean rats was not changed by pioglitazone. Tyrosine 32-40 insulin receptor substrate 1 Rattus norvegicus 67-72 8665940-1 1996 Tumor necrosis factor-alpha (TNF-alpha) is a proposed mediator of insulin resistance in obese/diabetic animals through its effects on tyrosine phosphorylation of the insulin receptor and its substrate, insulin receptor substrate-1. Tyrosine 134-142 insulin receptor substrate 1 Rattus norvegicus 202-230 8866828-4 1996 Both insulin (100 nM) and pervanadate (100 microM), a protein tyrosine phosphatase inhibitor, induced a marked increase in the phosphorylation at tyrosine residues of IR and insulin receptor substrate 1 (IRS-1) and in 2-deoxyglucose uptake in 3T3-L1 adipocytes. Tyrosine 62-70 insulin receptor substrate 1 Rattus norvegicus 204-209 8557682-3 1996 Consistent with a receptor level effect, in vivo insulin-dependent tyrosine phosphorylation of both IRS-1 and Shc was increased by a similar 3-fold with LAR suppression. Tyrosine 67-75 insulin receptor substrate 1 Rattus norvegicus 100-105 7588273-5 1995 To address this issue, we constructed different rat IRS-1 mutants containing mutations in the tyrosine residues that interact with the SH2 domains of PI3-K and PTP2C in vitro. Tyrosine 94-102 insulin receptor substrate 1 Rattus norvegicus 52-57 7559552-1 1995 Possible mechanism for suppression of insulin-stimulated tyrosine phosphorylation of IRS-1. Tyrosine 57-65 insulin receptor substrate 1 Rattus norvegicus 85-90 7559552-3 1995 We have previously shown that TNF diminishes insulin-induced tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1). Tyrosine 61-69 insulin receptor substrate 1 Rattus norvegicus 89-117 7559552-3 1995 We have previously shown that TNF diminishes insulin-induced tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1). Tyrosine 61-69 insulin receptor substrate 1 Rattus norvegicus 119-124 7559552-8 1995 TNF effect on IRS-1 tyrosine phosphorylation was not abolished by inhibiting protein kinase C using staurosporine, while inactivation of Ser/Thr phosphatases by calyculin A and okadaic acid mimicked it. Tyrosine 20-28 insulin receptor substrate 1 Rattus norvegicus 14-19 7559552-9 1995 Our data suggest that TNF induces serine phosphorylation of IRS-1 through inhibition of serine phosphatases or activation of serine kinases other than protein kinase C. This increased serine phosphorylation interferes with insulin-induced tyrosine phosphorylation of IRS-1 and impairs insulin action. Tyrosine 239-247 insulin receptor substrate 1 Rattus norvegicus 60-65 7862167-5 1995 We have reconstituted the IL-4 receptor into an insulin-responsive L6 myoblast cell line and have shown that IRS-1 is tyrosine phosphorylated to similar degrees in response to insulin and IL-4 stimulation in this cell line. Tyrosine 118-126 insulin receptor substrate 1 Rattus norvegicus 109-114 7526037-5 1994 The effect of ethanol on IGF-1 receptor and insulin receptor substrate 1 (IRS-1) tyrosine phosphorylation was determined by immunoprecipitation and Western blotting, as was the phosphatidylinositol 3-kinase content within IRS-1 immunoprecipitates. Tyrosine 81-89 insulin receptor substrate 1 Rattus norvegicus 44-72 7876077-0 1995 Growth hormone stimulates the tyrosine phosphorylation of the insulin receptor substrate-1 and its association with phosphatidylinositol 3-kinase in primary adipocytes. Tyrosine 30-38 insulin receptor substrate 1 Rattus norvegicus 62-90 7876077-1 1995 Insulin receptor substrate-1 (IRS-1) is tyrosine-phosphorylated in response to insulin resulting in association with and activation of phosphatidylinositol 3-kinase (PI 3-kinase), thereby initiating some of the effects of insulin. Tyrosine 40-48 insulin receptor substrate 1 Rattus norvegicus 0-28 7876077-1 1995 Insulin receptor substrate-1 (IRS-1) is tyrosine-phosphorylated in response to insulin resulting in association with and activation of phosphatidylinositol 3-kinase (PI 3-kinase), thereby initiating some of the effects of insulin. Tyrosine 40-48 insulin receptor substrate 1 Rattus norvegicus 30-35 7876077-7 1995 Here we show that IRS-1 is tyrosine-phosphorylated in a time- and dose-dependent manner in response to GH in primary rat adipocytes. Tyrosine 27-35 insulin receptor substrate 1 Rattus norvegicus 18-23 7876077-10 1995 Our data suggest that GH-induced tyrosine phosphorylation of IRS-1 and the subsequent docking of PI 3-kinase are important postreceptor events in GH action. Tyrosine 33-41 insulin receptor substrate 1 Rattus norvegicus 61-66 7961991-8 1994 The inhibitory effect of cytochalasin D treatment on the insulin stimulation of glucose transport occurred downstream of tyrosine phosphorylation of the insulin receptor substrate-1 and of binding of phosphatidylinositol 3-kinase to the insulin receptor substrate-1. Tyrosine 121-129 insulin receptor substrate 1 Rattus norvegicus 153-181 7965046-2 1994 Following tyrosine phosphorylation IRS-1 binds to and activates specific proteins containing SH2 domains. Tyrosine 10-18 insulin receptor substrate 1 Rattus norvegicus 35-40 7828547-6 1995 In response to IGF-1, insulin receptor substrate-1 was tyrosine phosphorylated and formed a complex with the PI3K heterodimer that consists of a p85 regulatory subunit and a p110 catalytic subunit. Tyrosine 55-63 insulin receptor substrate 1 Rattus norvegicus 22-50 7526037-5 1994 The effect of ethanol on IGF-1 receptor and insulin receptor substrate 1 (IRS-1) tyrosine phosphorylation was determined by immunoprecipitation and Western blotting, as was the phosphatidylinositol 3-kinase content within IRS-1 immunoprecipitates. Tyrosine 81-89 insulin receptor substrate 1 Rattus norvegicus 74-79 7526037-11 1994 Ethanol also interfered with the IGF-1-induced tyrosine phosphorylation of IRS-1, and the association of phosphatidylinositol-3 kinase with IRS-1. Tyrosine 47-55 insulin receptor substrate 1 Rattus norvegicus 75-80 7511094-1 1994 IRS-1 is phosphorylated on tyrosine residues after insulin stimulation and participates in the early events of signal transduction in peripheral insulin-sensitive tissues. Tyrosine 27-35 insulin receptor substrate 1 Rattus norvegicus 0-5 7527025-10 1994 Antiserum to IRS-1 immunoprecipitated the tyrosine-phosphorylated 185-kDa protein. Tyrosine 42-50 insulin receptor substrate 1 Rattus norvegicus 13-18 8175658-7 1994 These data suggest that: 1) p62 GAP-associated protein is tyrosine phosphorylated after insulin stimulation of cells; 2) p62 and IRS-1 form separate complexes with p85; 3) p62-GAP complex may be linked to p85 that is not bound to p110; 4) p85 may serve as an adaptor molecule in insulin receptor signaling, interacting with and regulating other intracellular proteins via SH2 domains. Tyrosine 58-66 insulin receptor substrate 1 Rattus norvegicus 129-134 8087096-2 1994 Insulin stimulates tyrosine phosphorylation of the insulin receptor and of an endogenous substrate of approximately 185 kDa (insulin receptor substrate 1 or IRS-1). Tyrosine 19-27 insulin receptor substrate 1 Rattus norvegicus 125-153 8087096-2 1994 Insulin stimulates tyrosine phosphorylation of the insulin receptor and of an endogenous substrate of approximately 185 kDa (insulin receptor substrate 1 or IRS-1). Tyrosine 19-27 insulin receptor substrate 1 Rattus norvegicus 157-162 8087096-3 1994 IRS-1 fulfills the criteria of a direct substrate of the insulin receptor, and tyrosine phosphorylation of IRS-1 leads to another step in insulin action, i.e., an association of phosphorylated IRS-1 with the enzyme PI3-kinase activating this enzyme. Tyrosine 79-87 insulin receptor substrate 1 Rattus norvegicus 107-112 8087096-3 1994 IRS-1 fulfills the criteria of a direct substrate of the insulin receptor, and tyrosine phosphorylation of IRS-1 leads to another step in insulin action, i.e., an association of phosphorylated IRS-1 with the enzyme PI3-kinase activating this enzyme. Tyrosine 79-87 insulin receptor substrate 1 Rattus norvegicus 107-112 8253716-3 1993 Incubation of the insulin-sensitive rat hepatoma Fao cells with 5 nM TNF for 1 h led to a 65% decrease in insulin-induced tyrosine phosphorylation of both the insulin receptor beta-subunit and IRS-1, its major cytosolic substrate. Tyrosine 122-130 insulin receptor substrate 1 Rattus norvegicus 159-198 7513124-1 1994 Insulin treatment of adipocytes causes the rapid phosphorylation of the insulin receptor substrate-1 (IRS-1) on tyrosine. Tyrosine 112-120 insulin receptor substrate 1 Rattus norvegicus 72-100 7513124-1 1994 Insulin treatment of adipocytes causes the rapid phosphorylation of the insulin receptor substrate-1 (IRS-1) on tyrosine. Tyrosine 112-120 insulin receptor substrate 1 Rattus norvegicus 102-107 7513124-2 1994 The phosphotyrosine [Tyr(P)] form of IRS-1 then complexes with the enzyme phosphatidylinositol (PI) 3-kinase. Tyrosine 21-24 insulin receptor substrate 1 Rattus norvegicus 37-42 7513124-7 1994 Moreover, the purified Tyr(P) form of IRS-1, either isolated from 3T3-L1 adipocytes or obtained by phosphorylation of the recombinant protein with the insulin receptor, markedly stimulated the activity of purified rat liver PI 3-kinase. Tyrosine 23-26 insulin receptor substrate 1 Rattus norvegicus 38-43 7513124-8 1994 These results show that the association of Tyr(P) IRS-1 with PI 3-kinase activates the enzyme and thereby can explain the elevation of PI 3,4-bisphosphate and PI 3,4,5-trisphosphate in vivo observed upon treatment of adipocytes with insulin. Tyrosine 43-46 insulin receptor substrate 1 Rattus norvegicus 50-55 7505468-1 1993 In peripheral insulin-sensitive tissues, insulin receptor substrate (IRS-1) undergoes tyrosine phosphorylation immediately after cells are stimulated by insulin or insulin-like growth factor-1 (IGF-1), and may function as a molecular link between insulin/IGF-1 receptor tyrosine kinases and enzymes regulating cell growth and metabolism. Tyrosine 86-94 insulin receptor substrate 1 Rattus norvegicus 69-74 8226726-3 1993 Furthermore, the antisense IRS-1 cell lines had decreased insulin-stimulated IRS-1 tyrosine phosphorylation, reduced phosphatidylinositol 3-kinase activation, and decreased thymidine incorporation relative to the parental cell line. Tyrosine 83-91 insulin receptor substrate 1 Rattus norvegicus 27-32 8226726-6 1993 Thus, the inhibition in insulin signaling was a specific effect of decreased IRS-1 tyrosine phosphorylation. Tyrosine 83-91 insulin receptor substrate 1 Rattus norvegicus 77-82 7683695-0 1993 Glucocorticoid regulation of insulin receptor and substrate IRS-1 tyrosine phosphorylation in rat skeletal muscle in vivo. Tyrosine 66-74 insulin receptor substrate 1 Rattus norvegicus 60-65 8349691-1 1993 IRS-1, a principal substrate of the insulin receptor, is phosphorylated on serine, threonine, and tyrosine residues in a variety of tissues during insulin stimulation. Tyrosine 98-106 insulin receptor substrate 1 Rattus norvegicus 0-5 7686484-3 1993 In the case of insulin, this activation is due to the tyrosine phosphorylation of its major cellular substrate, IRS-1. Tyrosine 54-62 insulin receptor substrate 1 Rattus norvegicus 112-117 8383963-7 1993 Both IRS-1 and the insulin-receptor beta-subunit (95 kDa) were phosphorylated on tyrosine residues by insulin stimulation and immunoprecipitated with anti-pTyr. Tyrosine 81-89 insulin receptor substrate 1 Rattus norvegicus 5-10 8382701-1 1993 Association with a 185-kDa tyrosine-phosphorylated protein (IRS-1) and localization in a low density membrane vesicle. Tyrosine 27-35 insulin receptor substrate 1 Rattus norvegicus 60-65 1385396-2 1992 Insulin rapidly stimulates tyrosine phosphorylation of its endogenous substrate, insulin receptor substrate 1 (IRS-1), and in vitro IRS-1 associates with PI 3-kinase, thus activating the enzyme. Tyrosine 27-35 insulin receptor substrate 1 Rattus norvegicus 81-109 1385403-7 1992 Expression of the human insulin receptor and rat IRS-1 together in CHO/IR/IRS-1 cells increased the basal serine phosphorylation of IRS-1 and strongly increased tyrosine phosphorylation during insulin stimulation. Tyrosine 161-169 insulin receptor substrate 1 Rattus norvegicus 49-54 8144649-5 1994 To explore the early signaling events that might account for this increase in responsiveness, we evaluated the tyrosine phosphorylation of the insulin receptor substrate, IRS-1, and its subsequent association with phosphatidylinositol (PI)-3 kinase. Tyrosine 111-119 insulin receptor substrate 1 Rattus norvegicus 171-176 8144649-6 1994 In both cell types, insulin led to a dose-dependent increase in the association of tyrosine phosphorylated IRS-1 with the SH2 domain of the p85 regulatory subunit of PI-3 kinase, and also increased the amount of PI kinase activity detected in anti-IRS-1 immunoprecipitates. Tyrosine 83-91 insulin receptor substrate 1 Rattus norvegicus 107-112 1385396-2 1992 Insulin rapidly stimulates tyrosine phosphorylation of its endogenous substrate, insulin receptor substrate 1 (IRS-1), and in vitro IRS-1 associates with PI 3-kinase, thus activating the enzyme. Tyrosine 27-35 insulin receptor substrate 1 Rattus norvegicus 111-116 1457763-1 1992 Insulin stimulates tyrosine phosphorylation of the insulin receptor and of an endogenous substrate of approximately 185 kd (insulin receptor substrate 1 or IRS-1) in most cell types. Tyrosine 19-27 insulin receptor substrate 1 Rattus norvegicus 124-152 1457763-1 1992 Insulin stimulates tyrosine phosphorylation of the insulin receptor and of an endogenous substrate of approximately 185 kd (insulin receptor substrate 1 or IRS-1) in most cell types. Tyrosine 19-27 insulin receptor substrate 1 Rattus norvegicus 156-161 33824679-10 2021 The level of IRS-1 tyrosine phosphorylation at Tyr895 sites was compared, and the result showed that there was no significant difference between the electroacupuncture group and the control group (P > 0.05), and the electroacupuncture group had higher phosphorylation expression than the model group (P < 0.05). Tyrosine 19-27 insulin receptor substrate 1 Rattus norvegicus 13-18 1382584-5 1992 IRS-1 and pp185 undergo tyrosine phosphorylation immediately after insulin stimulation and show an insulin dose response similar to that of insulin receptor autophosphorylation. Tyrosine 24-32 insulin receptor substrate 1 Rattus norvegicus 0-5 1382584-5 1992 IRS-1 and pp185 undergo tyrosine phosphorylation immediately after insulin stimulation and show an insulin dose response similar to that of insulin receptor autophosphorylation. Tyrosine 24-32 insulin receptor substrate 1 Rattus norvegicus 10-15 2022647-1 1991 Insulin stimulates the tyrosine phosphorylation of a 185-kDa putative cytosolic substrate protein (pp185) in diverse cell types. Tyrosine 23-31 insulin receptor substrate 1 Rattus norvegicus 99-104 2022647-2 1991 After intravenous insulin infusion into the live intact rat, pp185 and the 95-kDa insulin receptor beta-subunit were the major proteins that tyrosine phosphorylated in liver, skeletal muscle, and adipose tissue. Tyrosine 141-149 insulin receptor substrate 1 Rattus norvegicus 61-66 2022647-4 1991 However, pp185 tyrosine phosphorylation was transient, with almost complete dephosphorylation within 2-3 min despite continued insulin stimulation. Tyrosine 15-23 insulin receptor substrate 1 Rattus norvegicus 9-14 2022647-9 1991 These results indicate that pp185 is expressed in a variety of insulin-responsive tissues, is the major protein rapidly tyrosine phosphorylated under physiological conditions in the intact animal, and also provide a route for cloning the pp185 gene and elucidating the function of pp185 in insulin signal transduction. Tyrosine 120-128 insulin receptor substrate 1 Rattus norvegicus 28-33 2022647-9 1991 These results indicate that pp185 is expressed in a variety of insulin-responsive tissues, is the major protein rapidly tyrosine phosphorylated under physiological conditions in the intact animal, and also provide a route for cloning the pp185 gene and elucidating the function of pp185 in insulin signal transduction. Tyrosine 120-128 insulin receptor substrate 1 Rattus norvegicus 238-243 2022647-9 1991 These results indicate that pp185 is expressed in a variety of insulin-responsive tissues, is the major protein rapidly tyrosine phosphorylated under physiological conditions in the intact animal, and also provide a route for cloning the pp185 gene and elucidating the function of pp185 in insulin signal transduction. Tyrosine 120-128 insulin receptor substrate 1 Rattus norvegicus 238-243 1381348-3 1992 IN this model system, H/V treatment and, to a lesser extent, injection of insulin resulted in rapid and sustained tyrosine phosphorylation of multiple cellular proteins, including pp185/IRS-1. Tyrosine 114-122 insulin receptor substrate 1 Rattus norvegicus 180-185 1381348-3 1992 IN this model system, H/V treatment and, to a lesser extent, injection of insulin resulted in rapid and sustained tyrosine phosphorylation of multiple cellular proteins, including pp185/IRS-1. Tyrosine 114-122 insulin receptor substrate 1 Rattus norvegicus 186-191 1381348-5 1992 As p85 alpha was not detectably phosphorylated on tyrosine residues and did not appear to interact directly with the insulin receptor, we conclude that tyrosine phosphorylation of pp185 promotes its association with p85 alpha and the catalytic subunit of PI3K. Tyrosine 152-160 insulin receptor substrate 1 Rattus norvegicus 180-185 33824679-13 2021 The mechanism is related to the regulation of skeletal muscle IRS-1 serine/threonine and tyrosine phosphorylation levels. Tyrosine 89-97 insulin receptor substrate 1 Rattus norvegicus 62-67 15322693-7 2004 The levels of IRS-1 tyrosine phosphorylation, PI 3-kinase activity associated with IRS-1 and PKB activation after stimulation with insulin in muscle tissue of NIDDM rats were significantly decreased (P<0.01) compared with those in the control rats, while they were not increased by losartan. Tyrosine 20-28 insulin receptor substrate 1 Rattus norvegicus 14-19 35625574-8 2022 The effect of insulin on 2-deoxyglucose uptake by adipose tissue was impaired in obese rats which was accompanied by lower insulin-induced tyrosine phosphorylation of IRS-1 and Akt. Tyrosine 139-147 insulin receptor substrate 1 Rattus norvegicus 167-172 30486685-5 2020 Activation of JNK, NFkappaB, p38MAPK and insulin signaling from tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and serine phosphorylation of Akt were assessed in myotubes after Malathion exposure by western blot and was compared with those in controls. Tyrosine 64-72 insulin receptor substrate 1 Rattus norvegicus 92-120 2468662-0 1989 Tyrosine phosphorylation of pp185 by insulin receptor kinase in a cell-free system. Tyrosine 0-8 insulin receptor substrate 1 Rattus norvegicus 28-33 2468662-1 1989 Insulin treatment of rat H-35 hepatoma cells causes rapid tyrosine phosphorylation of a high molecular weight protein termed pp185 besides autophosphorylation of the beta-subunit of the insulin receptor (IR) in an intact cell system. Tyrosine 58-66 insulin receptor substrate 1 Rattus norvegicus 125-130 2468662-2 1989 To elucidate the molecular basis for tyrosine phosphorylation of pp185, cell-free phosphorylation of pp185 was performed using phosphotyrosine-containing proteins (PYPs) purified from detergent-solubilized cell lysates by immunoprecipitation with anti-phosphotyrosine antibody. Tyrosine 37-45 insulin receptor substrate 1 Rattus norvegicus 65-70 2468662-3 1989 After insulin treatment of cells, marked increases of tyrosine phosphorylation of pp185 and IR were observed compared to noninsulin-treated cells. Tyrosine 54-62 insulin receptor substrate 1 Rattus norvegicus 82-87 2468662-4 1989 Site-specific antibodies that specifically inactivate IR kinase inhibited tyrosine phosphorylation of pp185 as well as the beta-subunit of IR. Tyrosine 74-82 insulin receptor substrate 1 Rattus norvegicus 102-107 2468662-5 1989 PYPs purified from detergent-free cell extracts contained pp185 but little IR; tyrosine phosphorylation of pp185 did not occur. Tyrosine 79-87 insulin receptor substrate 1 Rattus norvegicus 107-112 2468662-6 1989 Addition of IR kinase purified from human placenta to these PYPs restored insulin-dependent tyrosine phosphorylation of pp185. Tyrosine 92-100 insulin receptor substrate 1 Rattus norvegicus 120-125 2468662-7 1989 These results suggest that tyrosine phosphorylation of pp185 is catalyzed directly by IR kinase in this cell-free system. Tyrosine 27-35 insulin receptor substrate 1 Rattus norvegicus 55-60 2439512-2 1987 In Fao cells, besides the beta-subunit of the insulin receptor, a protein with a molecular mass between 170 and 210 kDa designated pp185, undergoes tyrosine phosphorylation immediately after insulin stimulation reaching a maximum level within 30 s. After 4 h of continuous insulin stimulation, the labeling of pp185 decreased to less than half of its original intensity, whereas the insulin receptor was unchanged. Tyrosine 148-156 insulin receptor substrate 1 Rattus norvegicus 131-136 2439512-10 1987 Increasing the concentration of the human insulin receptor in the Chinese hamster ovary cells by transfection with a plasmid containing the human insulin receptor cDNA caused a higher level of tyrosine phosphorylation of the beta-subunit and the pp185. Tyrosine 193-201 insulin receptor substrate 1 Rattus norvegicus 246-251 30486685-5 2020 Activation of JNK, NFkappaB, p38MAPK and insulin signaling from tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and serine phosphorylation of Akt were assessed in myotubes after Malathion exposure by western blot and was compared with those in controls. Tyrosine 64-72 insulin receptor substrate 1 Rattus norvegicus 122-127 29955954-5 2019 RESULTS: Adding both EWH and IRW significantly improved glucose uptake in TNF-alpha-treated cells, increased activation of insulin receptor substrate (IRS-1) tyrosine residue and protein kinase B (Akt), whereas decreased activation of IRS-1 serine residue. Tyrosine 158-166 insulin receptor substrate 1 Rattus norvegicus 151-156 28324067-9 2017 In gastrocnemius muscles, LP rats showed reduced tyrosine phosphorylation of insulin receptor substrate 1 upon insulin stimulation due to the overexpression of tyrosine phosphatase SHP-2, but serine phosphorylation was unaffected. Tyrosine 49-57 insulin receptor substrate 1 Rattus norvegicus 77-105 31113619-6 2019 Moreover, tyrosine phosphorylation of the IR and IRS-1, and Akt activation is decreased in STZ diabetes compared to control. Tyrosine 10-18 insulin receptor substrate 1 Rattus norvegicus 49-54 31122091-7 2019 The level of tyrosine phosphorylation of insulin receptor substrate 1 and serine phosphorylation of protein kinase B (Akt) on insulin stimulation decreased in myotubes with exposure to subtoxic concentrations of DDT, but there was no change in tyrosine phosphorylation level of insulin receptors. Tyrosine 13-21 insulin receptor substrate 1 Rattus norvegicus 41-69 30918868-5 2018 Assessment of activation of NFkappaB & p38MAPK and insulin signaling following insulin stimulation from tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and serine phosphorylation of Akt were done in myotubes after chlorpyrifos exposure by western blot (WB) and compared with those in vehicle-treated controls. Tyrosine 108-116 insulin receptor substrate 1 Rattus norvegicus 136-164 29721029-0 2018 Effects of Modified Sanzi Yangqin Decoction on Tyrosine Phosphorylation of IRS-1 in Skeletal Muscle of Type 2 Diabetic Rats. Tyrosine 47-55 insulin receptor substrate 1 Rattus norvegicus 75-80 29721029-1 2018 This study aimed to investigate the effect of Modified Sanzi Yangqin Decoction on tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) in skeletal muscle of type 2 diabetic rats. Tyrosine 82-90 insulin receptor substrate 1 Rattus norvegicus 110-138 29721029-1 2018 This study aimed to investigate the effect of Modified Sanzi Yangqin Decoction on tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) in skeletal muscle of type 2 diabetic rats. Tyrosine 82-90 insulin receptor substrate 1 Rattus norvegicus 140-145 29721029-9 2018 Modified Sanzi Yangqin Decoction increases tyrosine phosphorylation of IRS-1 in skeletal muscle of type 2 diabetic rats, which results from the increase of p-IRS-1(Tyr895) protein and is related to the suppression of PTP1B protein. Tyrosine 43-51 insulin receptor substrate 1 Rattus norvegicus 71-76 29721029-9 2018 Modified Sanzi Yangqin Decoction increases tyrosine phosphorylation of IRS-1 in skeletal muscle of type 2 diabetic rats, which results from the increase of p-IRS-1(Tyr895) protein and is related to the suppression of PTP1B protein. Tyrosine 43-51 insulin receptor substrate 1 Rattus norvegicus 158-163 29248832-6 2018 Furthermore, hepatic translational analyses revealed sensitization on proximal insulin signalling, with reduced expression of IRS1 serine phosphorylation, increased IRS1 tyrosine phosphorylation and increased phospho-AKT (Ser473). Tyrosine 170-178 insulin receptor substrate 1 Rattus norvegicus 165-169 27180072-5 2017 In addition to IGF-1, the relative expression of insulin receptor substrate-1 (IRS1) phosphorylated at the tyrosine residue (p-IRS1tyr), phosphorylated protein kinase B (p-AKT) and phosphorylated protein kinase A (p-PKA), which are involved in IGF-1 signalling, was also studied in hypoxic retinas and in cultured RGCs. Tyrosine 107-115 insulin receptor substrate 1 Rattus norvegicus 49-77 27180072-5 2017 In addition to IGF-1, the relative expression of insulin receptor substrate-1 (IRS1) phosphorylated at the tyrosine residue (p-IRS1tyr), phosphorylated protein kinase B (p-AKT) and phosphorylated protein kinase A (p-PKA), which are involved in IGF-1 signalling, was also studied in hypoxic retinas and in cultured RGCs. Tyrosine 107-115 insulin receptor substrate 1 Rattus norvegicus 79-83 31001119-8 2019 In addition, Cand also mitigated the LPS-induced disturbance of insulin signaling with the normalized phosphorylation of serine 307 and tyrosine 896 of insulin receptor substrate-1 (IRS-1). Tyrosine 136-144 insulin receptor substrate 1 Rattus norvegicus 152-180 31001119-8 2019 In addition, Cand also mitigated the LPS-induced disturbance of insulin signaling with the normalized phosphorylation of serine 307 and tyrosine 896 of insulin receptor substrate-1 (IRS-1). Tyrosine 136-144 insulin receptor substrate 1 Rattus norvegicus 182-187 30248393-6 2019 HSP70 was induced and insulin signaling as measured from tyrosine phosphorylation of insulin receptor (IR) & insulin receptor substrate-1 (IRS-1) and serine phosphorylation of Akt was attenuated in comparison to those in untreated myotubes. Tyrosine 57-65 insulin receptor substrate 1 Rattus norvegicus 113-141 30248393-6 2019 HSP70 was induced and insulin signaling as measured from tyrosine phosphorylation of insulin receptor (IR) & insulin receptor substrate-1 (IRS-1) and serine phosphorylation of Akt was attenuated in comparison to those in untreated myotubes. Tyrosine 57-65 insulin receptor substrate 1 Rattus norvegicus 143-148 30620715-13 2019 IRS1 phosphorylation was measured in tyrosine residues, which activates the pathway, and in serine residues, which impairs insulin action. Tyrosine 37-45 insulin receptor substrate 1 Rattus norvegicus 0-4 27619406-4 2017 Consequently, NaBut induced Irs1 mRNA and protein overexpression, which in turn relayed higher insulin-stimulated IRS1 tyrosine phosphorylation and PI 3-kinase (phosphoinositide 3-kinase) association, suggesting that the increased IRS1 expression may mediate the insulin-sensitizing effects of NaBut. Tyrosine 119-127 insulin receptor substrate 1 Rattus norvegicus 114-118 28063625-9 2017 We demonstrated that the favorable effect of antidepressans on insulin receptor phosphorylation in the frontal cortex was mainly related with the normalization of serine312 and tyrosine IRS-1 phosphorylation, while in the hippocampus, it was related with the adaptor proteins Shc1/Grb2. Tyrosine 177-185 insulin receptor substrate 1 Rattus norvegicus 186-191 26713546-4 2016 Curcumin treatment attenuated the insulin resistance by decreasing IRS-1 serine phosphorylation and increasing IRS-1 tyrosine phosphorylation in the skeletal muscle of high fructose fed rats. Tyrosine 117-125 insulin receptor substrate 1 Rattus norvegicus 111-116 26099503-10 2016 Compared with control cells, INS-1 cells overexpressing PTP1B showed decrease in insulin-stimulated tyrosine phosphorylation of the insulin receptor (IR) and insulin receptor substrate-1(IRS-1) by 56.4% and 53.1%, respectively. Tyrosine 100-108 insulin receptor substrate 1 Rattus norvegicus 187-192 25779204-9 2015 Tyrosine nitration of the insulin receptor substrate-1 (IRS-1) was increased. Tyrosine 0-8 insulin receptor substrate 1 Rattus norvegicus 26-54 26644274-10 2016 Exercise managed to prevent most of the disturbances in insulin signaling caused by fructose diet (except phosphorylation of IRS1 at Tyr 632 and phosphorylation and protein expression of ERK1/2) and consequently restored function of eNOS. Tyrosine 133-136 insulin receptor substrate 1 Rattus norvegicus 125-129 25779204-9 2015 Tyrosine nitration of the insulin receptor substrate-1 (IRS-1) was increased. Tyrosine 0-8 insulin receptor substrate 1 Rattus norvegicus 56-61 25779204-11 2015 Collectively, these findings indicate that cLDL, alone, attenuates glucose uptake via NO-mediated tyrosine nitration of IRS-1 in L6 rat muscle cells and suggests the possibility that cLDL is involved in the pathogenesis of T2DM. Tyrosine 98-106 insulin receptor substrate 1 Rattus norvegicus 120-125 26084330-7 2015 The phosphorylation of tyrosine, which is upstream of Akt, in insulin receptor substrate-1 (IRS-1) was increased by the L-Cit treatment. Tyrosine 23-31 insulin receptor substrate 1 Rattus norvegicus 62-90 26084330-7 2015 The phosphorylation of tyrosine, which is upstream of Akt, in insulin receptor substrate-1 (IRS-1) was increased by the L-Cit treatment. Tyrosine 23-31 insulin receptor substrate 1 Rattus norvegicus 92-97 23749991-4 2013 In PC12 cells, tyrosine phosphorylation of INSR and IRS-1 is dependent upon the functional TrkA kinase domain. Tyrosine 15-23 insulin receptor substrate 1 Rattus norvegicus 52-57 25730774-6 2015 Insulin-stimulated tyrosine phosphorylation of insulin receptor substrate 1 (IRS1) was reduced significantly in the liver tissue of MI rats compared with controls, followed by decreased attachment of phosphatidylinositol 3-kinase (PI3K) p85 subunit with IRS1 and Akt phosphorylation. Tyrosine 19-27 insulin receptor substrate 1 Rattus norvegicus 77-81 25730774-6 2015 Insulin-stimulated tyrosine phosphorylation of insulin receptor substrate 1 (IRS1) was reduced significantly in the liver tissue of MI rats compared with controls, followed by decreased attachment of phosphatidylinositol 3-kinase (PI3K) p85 subunit with IRS1 and Akt phosphorylation. Tyrosine 19-27 insulin receptor substrate 1 Rattus norvegicus 254-258 24845581-8 2014 In vitro mechanistic study in neonatal rat cardiomyocytes revealed that insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and Akt was significantly attenuated by high glucose, accompanied by markedly increased IRS-1 O-GlcNAc glycosylation following hypoxia/reoxygenation. Tyrosine 91-99 insulin receptor substrate 1 Rattus norvegicus 149-154 24437486-5 2014 The basal and insulin-stimulated tyrosine phosphorylation of IRS-1 and AKT proteins was reduced. Tyrosine 33-41 insulin receptor substrate 1 Rattus norvegicus 61-66 24437486-8 2014 In contrast, the phosphorylated IRS-1 at tyrosine site and AKT levels were partially restored with improved poststroke hyperglycemia and insulin resistance index. Tyrosine 41-49 insulin receptor substrate 1 Rattus norvegicus 32-37 24621780-10 2014 In WAT, 5C-feeding decreased tyrosine phosphorylation of IRS-1 compared to 15C-feeding. Tyrosine 29-37 insulin receptor substrate 1 Rattus norvegicus 57-62 23715867-7 2013 We observed astaxanthin enhanced insulin-stimulated GLUT4 translocation and glucose uptake, which was associated with an increase in insulin receptor substrate-1 tyrosine and Akt phosphorylation and a decrease in c-Jun N-terminal kinase (JNK) and insulin receptor substrate-1 serine 307 phosphorylation. Tyrosine 162-170 insulin receptor substrate 1 Rattus norvegicus 133-161 23279876-4 2013 For insulin signaling transduction, phosphorylation of insulin receptor (IR), insulin receptor substrate-1 (IRS1) at the tyrosine residue, Akt, and AMP-activated protein kinase (AMPK), were attenuated in the liver, while negative regulators of insulin action, including phosphorylation of p38, c-Jun N-terminal kinase (JNK), and insulin receptor substrate-1 (IRS1) at the serine residue, were increased. Tyrosine 121-129 insulin receptor substrate 1 Rattus norvegicus 78-106 23639626-4 2013 By "working upwards" from mTOR, we observed that TCDD inhibited endogenous and IGF-I-induced AKT and ERK activation by interfering with tyrosine phosphorylation of insulin receptor substrate 1. Tyrosine 136-144 insulin receptor substrate 1 Rattus norvegicus 164-192 23279876-4 2013 For insulin signaling transduction, phosphorylation of insulin receptor (IR), insulin receptor substrate-1 (IRS1) at the tyrosine residue, Akt, and AMP-activated protein kinase (AMPK), were attenuated in the liver, while negative regulators of insulin action, including phosphorylation of p38, c-Jun N-terminal kinase (JNK), and insulin receptor substrate-1 (IRS1) at the serine residue, were increased. Tyrosine 121-129 insulin receptor substrate 1 Rattus norvegicus 108-112 23279876-5 2013 In addition, the brains of rats with stroke exhibited a reduction in phosphorylation of IRS1 at the tyrosine residue and Akt. Tyrosine 100-108 insulin receptor substrate 1 Rattus norvegicus 88-92 22901685-3 2013 Genistein inhibited insulin-stimulated tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and attenuated downstream Akt and endothelial nitric oxide synthase (eNOS) phosphorylation, leading to a decreased nitric oxide (NO) production in endothelial cells. Tyrosine 39-47 insulin receptor substrate 1 Rattus norvegicus 97-102 22942179-4 2012 Tyrosine phosphorylation of insulin receptor-beta and insulin receptor substrate (IRS)-1 and phosphorylation of protein kinase B and endothelial nitric oxide synthase were all decreased in aorta from RRM rats, whereas serine phosphorylation of IRS-1, a marker of insulin resistance, was increased. Tyrosine 0-8 insulin receptor substrate 1 Rattus norvegicus 54-88 22982470-4 2012 IRS-1 concentration remained unchanged although IRS-1 tyrosine phosphorylation was decreased (P<0.05), and IRS-1 serine phosphorylation (pS) was increased (P<0.05) in obese animals compared to lean animals. Tyrosine 54-62 insulin receptor substrate 1 Rattus norvegicus 48-53 22982470-4 2012 IRS-1 concentration remained unchanged although IRS-1 tyrosine phosphorylation was decreased (P<0.05), and IRS-1 serine phosphorylation (pS) was increased (P<0.05) in obese animals compared to lean animals. Tyrosine 54-62 insulin receptor substrate 1 Rattus norvegicus 48-53 22187297-16 2012 Trauma induced Ser phosphorylation instead of Tyr phosphorylation eliminated the ability of IRS-1 to activate downstream effector molecules such as PKB/Akt and resulted in severe impairment of insulin signal transduction and glucose transport in skeletal muscle. Tyrosine 46-49 insulin receptor substrate 1 Rattus norvegicus 92-97 22314193-9 2012 Puerarin attenuated PA-induced phosphorylation of insulin receptor substrate-1 (IRS-1) at S307 and effectively ameliorated insulin-mediated tyrosine phosphorylation of IRS-1. Tyrosine 140-148 insulin receptor substrate 1 Rattus norvegicus 168-173 22314193-10 2012 The beneficial modification of serine/tyrosine phosphorylation of IRS-1 restored downstream Akt/eNOS activation, and thereby increased insulin-mediated NO production. Tyrosine 38-46 insulin receptor substrate 1 Rattus norvegicus 66-71 22138235-9 2012 In addition, taurine increased GLUT 4 translocation to the cardiac membrane by enhanced phosphorylation of IR and IRS1 at tyrosine and Akt at serine residue in the heart. Tyrosine 122-130 insulin receptor substrate 1 Rattus norvegicus 114-118 21618539-4 2012 Consistently, clozapine reduced insulin effect on insulin receptor (IR) by 40% and on IR substrate-1 (IRS1) tyrosine phosphorylation by 60%. Tyrosine 108-116 insulin receptor substrate 1 Rattus norvegicus 86-100 21618539-4 2012 Consistently, clozapine reduced insulin effect on insulin receptor (IR) by 40% and on IR substrate-1 (IRS1) tyrosine phosphorylation by 60%. Tyrosine 108-116 insulin receptor substrate 1 Rattus norvegicus 102-106 22233773-4 2012 Tyrosine phosphorylation of IR beta subunit, IRS-1 and Shc and phosphorylation of downstream components (Akt and MAPK ERK1/2) were significantly reduced as expected by fasting in rat, but not in chicken. Tyrosine 0-8 insulin receptor substrate 1 Rattus norvegicus 28-50 21602124-8 2011 CONCLUSION: APN may decrease tyrosine phosphorylation of IRS-1 via the IKK/NFkappaB pathway and inhibit insulin signaling pathway in the liver, which contributes to hyperlipidemia, hyperglycemia and development of type 2 diabetes. Tyrosine 29-37 insulin receptor substrate 1 Rattus norvegicus 57-62 21940847-10 2011 Intravenous injection of caffeine at a physiological dose (5 mg/kg) in rats inhibited the phosphorylation of insulin-stimulated IRS-1 Tyr(612) and Akt Ser(473) in epitrochlearis muscle. Tyrosine 134-137 insulin receptor substrate 1 Rattus norvegicus 128-133 21940847-6 2011 Blockade of IKK/IRS-1 Ser(307) by caffeic acid ameliorated the caffeine-induced downregulation of IRS-1 Tyr(612) phosphorylation and 3MG transport. Tyrosine 104-107 insulin receptor substrate 1 Rattus norvegicus 16-21 21940847-6 2011 Blockade of IKK/IRS-1 Ser(307) by caffeic acid ameliorated the caffeine-induced downregulation of IRS-1 Tyr(612) phosphorylation and 3MG transport. Tyrosine 104-107 insulin receptor substrate 1 Rattus norvegicus 98-103 20972939-6 2011 Further, combination therapy with NAT and TEL, but not each monotherapy alone, significantly restored the decrease in hepatic IRS-1 tyrosine phosphorylation in these animals. Tyrosine 132-140 insulin receptor substrate 1 Rattus norvegicus 126-131 21185755-9 2011 It also diminished insulin-stimulated tyrosine phosphorylation of IRS1 and serine phosphorylation of Akt without affecting the phosphorylation of IR, ERK1/2, p38, or JNK. Tyrosine 38-46 insulin receptor substrate 1 Rattus norvegicus 66-70 19686764-5 2009 Leptin increased tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) in the aortic wall, and this effect was impaired in obese and fructose-fed animals. Tyrosine 17-25 insulin receptor substrate 1 Rattus norvegicus 45-73 21072680-6 2011 It also diminished insulin-stimulated tyrosine phosphorylation of IRS-1, PI3K (p85), and serine phosphorylation of Akt without affecting the phosphorylation of IR, ERK1/2, P38, and JNK. Tyrosine 38-46 insulin receptor substrate 1 Rattus norvegicus 66-71 20596724-6 2010 IRS-1 tyrosine phosphorylation was increased (p < 0.05) and IRS-1 serine 307 phosphorylation was decreased (p < 0.05) in HFX compared to HF. Tyrosine 6-14 insulin receptor substrate 1 Rattus norvegicus 0-5 20801894-5 2010 In addition, protein deprivation caused an increase in protein levels of IR substrate 1 (IRS1) and IRS2, leading to the marked enhancement of insulin-induced tyrosine phosphorylation of IRS2 and its binding to the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3K). Tyrosine 158-166 insulin receptor substrate 1 Rattus norvegicus 73-87 20801894-5 2010 In addition, protein deprivation caused an increase in protein levels of IR substrate 1 (IRS1) and IRS2, leading to the marked enhancement of insulin-induced tyrosine phosphorylation of IRS2 and its binding to the p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3K). Tyrosine 158-166 insulin receptor substrate 1 Rattus norvegicus 89-93 20036710-5 2010 Berberine improved insulin-induced tyrosine-phosphorylation of IRS-1 and the recruitment of p85 to IRS-1. Tyrosine 35-43 insulin receptor substrate 1 Rattus norvegicus 63-68 20855122-6 2010 IH also increased JNK1 activity and insulin receptor substrate 1/2 (IRS-1/2) serine phosphorylation, reduced insulin-stimulated IRS-1/2 tyrosine phosphorylation and Akt serine 473 phosphorylation, and induced hepatic insulin resistance. Tyrosine 136-144 insulin receptor substrate 1 Rattus norvegicus 128-135 20388825-5 2010 Ad vector infection significantly reduced total levels of the insulin receptor (IR), and insulin receptor substrates 1 and 2 (IRS-1, IRS-2) in the liver of rats, resulting in decreased insulin-induced tyrosine phosphorylation of IR, IRS-1, and IRS-2, and decreased interaction of IRS-1 and IRS-2 with phosphoinositide 3-kinase (PI3K). Tyrosine 201-209 insulin receptor substrate 1 Rattus norvegicus 126-131 19686764-5 2009 Leptin increased tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) in the aortic wall, and this effect was impaired in obese and fructose-fed animals. Tyrosine 17-25 insulin receptor substrate 1 Rattus norvegicus 75-80 19386987-5 2009 IRS-1 tyrosine phosphorylation was decreased (P < 0.05), and IRS-1 serine 307 phosphorylation was increased (P < 0.05) in HF. Tyrosine 6-14 insulin receptor substrate 1 Rattus norvegicus 0-5 19781177-5 2009 IRS-1 protein and tyrosine phosphorylation of IRS-1 and Ser(307) phosphorylation of IRS-1 were detected by Western Blotting and immuno-precipitation. Tyrosine 18-26 insulin receptor substrate 1 Rattus norvegicus 46-51 19781177-7 2009 RESULTS: Tyrosine phosphorylation of IRS-1 in sepsis group was significantly lower than in control group (P < 0.01), while Ser(307) phosphorylation of IRS-1 in sepsis group was significantly higher than in control group (P < 0.01). Tyrosine 9-17 insulin receptor substrate 1 Rattus norvegicus 37-42 19781177-9 2009 There was significant negative correlation between activity of NF-kappaB and tyrosine phosphorylation of IRS-1 (r = 0.972, P < 0.01). Tyrosine 77-85 insulin receptor substrate 1 Rattus norvegicus 105-110 19781177-5 2009 IRS-1 protein and tyrosine phosphorylation of IRS-1 and Ser(307) phosphorylation of IRS-1 were detected by Western Blotting and immuno-precipitation. Tyrosine 18-26 insulin receptor substrate 1 Rattus norvegicus 46-51 19563078-7 2009 The phosphorylation of tyrosine (Tyr) residue of IRS-1 in the operation group was attenuated by 31% (P = 0.018), whereas the phosphorylation of serine (Ser) residue of IRS-1 was significantly enhanced by 63% compared with the control group (P = 0.000). Tyrosine 23-31 insulin receptor substrate 1 Rattus norvegicus 49-54 19563078-7 2009 The phosphorylation of tyrosine (Tyr) residue of IRS-1 in the operation group was attenuated by 31% (P = 0.018), whereas the phosphorylation of serine (Ser) residue of IRS-1 was significantly enhanced by 63% compared with the control group (P = 0.000). Tyrosine 33-36 insulin receptor substrate 1 Rattus norvegicus 49-54 19563078-7 2009 The phosphorylation of tyrosine (Tyr) residue of IRS-1 in the operation group was attenuated by 31% (P = 0.018), whereas the phosphorylation of serine (Ser) residue of IRS-1 was significantly enhanced by 63% compared with the control group (P = 0.000). Tyrosine 33-36 insulin receptor substrate 1 Rattus norvegicus 168-173 19563078-13 2009 Such impaired interactions abolished the ability of IRS-1 to undergo insulin-induced Tyr phosphorylation and further propagate the insulin receptor signal. Tyrosine 85-88 insulin receptor substrate 1 Rattus norvegicus 52-57 17942003-0 2008 Bitter gourd (Momordica charantia) improves insulin sensitivity by increasing skeletal muscle insulin-stimulated IRS-1 tyrosine phosphorylation in high-fat-fed rats. Tyrosine 119-127 insulin receptor substrate 1 Rattus norvegicus 113-118 18679708-7 2009 Shc tyrosine phosphorylation and activation of ERK1/2 were increased after reperfusion, while tyrosine phosphorylation of IRS-1 and activation of PKB/Akt were decreased. Tyrosine 94-102 insulin receptor substrate 1 Rattus norvegicus 122-127 18339717-7 2008 In addition, blockage of TNFR1-mediated TNF-alpha signaling in obese rats significantly enhanced tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) in the muscle and fat tissues. Tyrosine 97-105 insulin receptor substrate 1 Rattus norvegicus 125-153 18339717-7 2008 In addition, blockage of TNFR1-mediated TNF-alpha signaling in obese rats significantly enhanced tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1) in the muscle and fat tissues. Tyrosine 97-105 insulin receptor substrate 1 Rattus norvegicus 155-160 19263259-6 2009 Consistent with the clamp data, the extent of insulin receptor substrate (IRS)-1 tyrosine phosphorylation in response to insulin was significantly enhanced in the liver and adipose tissues. Tyrosine 81-89 insulin receptor substrate 1 Rattus norvegicus 46-80 19263259-8 2009 CONCLUSION: These results demonstrate that visfatin/PBEF/Nampt improves insulin sensitivity and exerts its hypocholesterolemic effects at least partially through upregulation of the tyrosine phosphorylation of IRS-1 protein and the mRNA levels of PPARgamma and SREBP-2. Tyrosine 182-190 insulin receptor substrate 1 Rattus norvegicus 210-215 18093209-4 2008 Exenatide also prevented HFD-induced deterioration in peripheral and hepatic insulin sensitivity, insulin clearance, glucose tolerance and decreased tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) in fat and skeletal muscles. Tyrosine 149-157 insulin receptor substrate 1 Rattus norvegicus 177-205 18093209-4 2008 Exenatide also prevented HFD-induced deterioration in peripheral and hepatic insulin sensitivity, insulin clearance, glucose tolerance and decreased tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) in fat and skeletal muscles. Tyrosine 149-157 insulin receptor substrate 1 Rattus norvegicus 207-212 18445755-7 2008 Along with increased soleus muscle NADPH oxidase activity and ROS, there was systemic insulin resistance and reduced muscle IRS-1 tyrosine phosphorylation, Akt phosphorylation/activation, and GLUT4 expression in the Ren2 group (each P < 0.05). Tyrosine 130-138 insulin receptor substrate 1 Rattus norvegicus 124-129 18385470-7 2008 In HFF plantaris muscle, in vivo insulin receptor beta-subunit (IR-beta) and insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation and phosphorylation of Akt Ser473 and glycogen synthase kinase-3beta (GSK-3beta) Ser9, relative to circulating insulin levels, were decreased by 40-59%. Tyrosine 114-122 insulin receptor substrate 1 Rattus norvegicus 77-105 18385470-7 2008 In HFF plantaris muscle, in vivo insulin receptor beta-subunit (IR-beta) and insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation and phosphorylation of Akt Ser473 and glycogen synthase kinase-3beta (GSK-3beta) Ser9, relative to circulating insulin levels, were decreased by 40-59%. Tyrosine 114-122 insulin receptor substrate 1 Rattus norvegicus 107-112 18385470-8 2008 In vitro insulin-stimulated glucose transport in HFF soleus was decreased by 54%, as were IRS-1 tyrosine phosphorylation (26%) and phosphorylation of Akt Ser473 (38%) and GSK-3beta Ser9 (25%), the latter indicative of GSK-3 overactivity. Tyrosine 96-104 insulin receptor substrate 1 Rattus norvegicus 90-95 18385470-9 2008 GSK-3 inhibition in HFF soleus using CT98014 increased insulin-stimulated glucose transport (28%), IRS-1 tyrosine phosphorylation (28%) and phosphorylation of Akt Ser473 (38%) and GSK-3beta Ser9 (48%). Tyrosine 105-113 insulin receptor substrate 1 Rattus norvegicus 99-104 18434358-5 2008 Fat feeding to rats for 9 weeks significantly increased IRS-1 serine phoshorylation, reduced insulin-stimulated IRS-1 tyrosine phosphorylation and insulin sensitivity. Tyrosine 118-126 insulin receptor substrate 1 Rattus norvegicus 112-117 18285345-3 2008 Phosphorylation of this site was simulated using IRS-1 Glu(357) and shown to reduce insulin-induced tyrosine phosphorylation of IRS-1, to decrease activation of Akt, and to subsequently diminish phosphorylation of glycogen synthase kinase-3. Tyrosine 100-108 insulin receptor substrate 1 Rattus norvegicus 49-54 18285345-3 2008 Phosphorylation of this site was simulated using IRS-1 Glu(357) and shown to reduce insulin-induced tyrosine phosphorylation of IRS-1, to decrease activation of Akt, and to subsequently diminish phosphorylation of glycogen synthase kinase-3. Tyrosine 100-108 insulin receptor substrate 1 Rattus norvegicus 128-133 17942003-6 2008 However high-fat feeding for 10 weeks reduced the insulin-stimulated IRS-1 tyrosine phosphorylation compared to control rats. Tyrosine 75-83 insulin receptor substrate 1 Rattus norvegicus 69-74 17942003-7 2008 Bitter gourd supplementation together with HFD for 2 weeks improved the insulin-stimulated IRS-1 tyrosine phosphorylation compared to rats fed with HFD alone. Tyrosine 97-105 insulin receptor substrate 1 Rattus norvegicus 91-96 17003331-5 2006 Investigation of insulin signaling revealed that bradykinin enhanced insulin receptor substrate-1 (IRS-1) Tyr phosphorylation, Akt/protein kinase B phosphorylation, and GLUT4 translocation. Tyrosine 106-109 insulin receptor substrate 1 Rattus norvegicus 69-97 18029440-7 2008 In fact, IkappaBKbeta overexpression in particular caused increases in activating tyrosine phosphorylation of insulin receptor substrate-1 (24%; P = 0.02) and serine phosphorylation of Akt (23%; P < 0.001), implying a moderate increase in flux through the insulin signaling cascade. Tyrosine 82-90 insulin receptor substrate 1 Rattus norvegicus 110-138 17823255-10 2007 Furthermore, the impaired insulin-stimulated tyrosine phosphorylation of IRS-1 in adipose tissue of pregnant animals could be restored ex vivo by treating isolated adipocytes with adiponectin. Tyrosine 45-53 insulin receptor substrate 1 Rattus norvegicus 73-78 17660951-6 2007 When 3T3-L1 adipocytes were treated directly with MG, the impaired insulin signaling was also observed, indicated by decreased insulin-induced insulin-receptor substrate-1 (IRS-1) tyrosine phosphorylation and the decreased kinase activity of phosphatidylinositol (PI) 3-kinase (PI3K). Tyrosine 180-188 insulin receptor substrate 1 Rattus norvegicus 173-178 17229938-3 2007 Upon JAK2 activation, tyrosine phosphorylation of insulin receptor substrate (IRS)-1 is detected. Tyrosine 22-30 insulin receptor substrate 1 Rattus norvegicus 50-84 17229938-6 2007 These data indicate a new signal transduction pathway for IRS-1/PI 3-kinase/Akt/eNOS activation and ERK1/2 by means of JAK2 tyrosine phosphorylation stimulated by ACh in vessels. Tyrosine 124-132 insulin receptor substrate 1 Rattus norvegicus 58-63 17303005-7 2007 Resistin also diminished insulin-stimulated IRS-1 tyrosine phosphorylation levels without affecting its protein content. Tyrosine 50-58 insulin receptor substrate 1 Rattus norvegicus 44-49 17403295-8 2007 The level of IRS-1 Serine 307 phosphorylation and phospho-JNK in muscle increased significantly, while insulin-induced tyrosine phosphorylation of IRS-1 decreased markedly after burn. Tyrosine 119-127 insulin receptor substrate 1 Rattus norvegicus 147-152 17438698-14 2006 The level of IRS-1 Serine307 phosphorylation and JNK activity in muscles were significantly increased, while insulin-induced tyrosine phosphorylation of IRS-1 decreased markedly after scald. Tyrosine 125-133 insulin receptor substrate 1 Rattus norvegicus 153-158 16873541-7 2006 The treatment with leptin also led to the tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and serine phosphorylation of Akt. Tyrosine 42-50 insulin receptor substrate 1 Rattus norvegicus 70-104 17579208-3 2007 Increases in RhoA/ROK activities and serine phosphorylation levels of insulin receptor substrate (IRS)-1 (Ser307 and Ser636/639) and IRS-2 were found in proliferating myoblasts, whereas IRS-1/2 tyrosine phosphorylation and phosphatidylinositol (PI) 3-kinase activity increased during the differentiation process. Tyrosine 194-202 insulin receptor substrate 1 Rattus norvegicus 70-104 17579213-7 2007 A S522(Irs1)-->A522(Irs1) substitution increased insulin-stimulated tyrosine phosphorylation of Irs1 and signaling, whereas a S522(Irs1)-->E522(Irs1) substitution reduced insulin-stimulated Irs1 tyrosine phosphorylation. Tyrosine 71-79 insulin receptor substrate 1 Rattus norvegicus 7-11 17579213-7 2007 A S522(Irs1)-->A522(Irs1) substitution increased insulin-stimulated tyrosine phosphorylation of Irs1 and signaling, whereas a S522(Irs1)-->E522(Irs1) substitution reduced insulin-stimulated Irs1 tyrosine phosphorylation. Tyrosine 71-79 insulin receptor substrate 1 Rattus norvegicus 23-27 17579213-7 2007 A S522(Irs1)-->A522(Irs1) substitution increased insulin-stimulated tyrosine phosphorylation of Irs1 and signaling, whereas a S522(Irs1)-->E522(Irs1) substitution reduced insulin-stimulated Irs1 tyrosine phosphorylation. Tyrosine 71-79 insulin receptor substrate 1 Rattus norvegicus 23-27 17579213-7 2007 A S522(Irs1)-->A522(Irs1) substitution increased insulin-stimulated tyrosine phosphorylation of Irs1 and signaling, whereas a S522(Irs1)-->E522(Irs1) substitution reduced insulin-stimulated Irs1 tyrosine phosphorylation. Tyrosine 71-79 insulin receptor substrate 1 Rattus norvegicus 23-27 17579213-7 2007 A S522(Irs1)-->A522(Irs1) substitution increased insulin-stimulated tyrosine phosphorylation of Irs1 and signaling, whereas a S522(Irs1)-->E522(Irs1) substitution reduced insulin-stimulated Irs1 tyrosine phosphorylation. Tyrosine 71-79 insulin receptor substrate 1 Rattus norvegicus 23-27 17579213-7 2007 A S522(Irs1)-->A522(Irs1) substitution increased insulin-stimulated tyrosine phosphorylation of Irs1 and signaling, whereas a S522(Irs1)-->E522(Irs1) substitution reduced insulin-stimulated Irs1 tyrosine phosphorylation. Tyrosine 71-79 insulin receptor substrate 1 Rattus norvegicus 23-27 17579213-7 2007 A S522(Irs1)-->A522(Irs1) substitution increased insulin-stimulated tyrosine phosphorylation of Irs1 and signaling, whereas a S522(Irs1)-->E522(Irs1) substitution reduced insulin-stimulated Irs1 tyrosine phosphorylation. Tyrosine 201-209 insulin receptor substrate 1 Rattus norvegicus 23-27 17579213-7 2007 A S522(Irs1)-->A522(Irs1) substitution increased insulin-stimulated tyrosine phosphorylation of Irs1 and signaling, whereas a S522(Irs1)-->E522(Irs1) substitution reduced insulin-stimulated Irs1 tyrosine phosphorylation. Tyrosine 201-209 insulin receptor substrate 1 Rattus norvegicus 23-27 17579213-7 2007 A S522(Irs1)-->A522(Irs1) substitution increased insulin-stimulated tyrosine phosphorylation of Irs1 and signaling, whereas a S522(Irs1)-->E522(Irs1) substitution reduced insulin-stimulated Irs1 tyrosine phosphorylation. Tyrosine 201-209 insulin receptor substrate 1 Rattus norvegicus 23-27 17579213-7 2007 A S522(Irs1)-->A522(Irs1) substitution increased insulin-stimulated tyrosine phosphorylation of Irs1 and signaling, whereas a S522(Irs1)-->E522(Irs1) substitution reduced insulin-stimulated Irs1 tyrosine phosphorylation. Tyrosine 201-209 insulin receptor substrate 1 Rattus norvegicus 23-27 17579213-7 2007 A S522(Irs1)-->A522(Irs1) substitution increased insulin-stimulated tyrosine phosphorylation of Irs1 and signaling, whereas a S522(Irs1)-->E522(Irs1) substitution reduced insulin-stimulated Irs1 tyrosine phosphorylation. Tyrosine 201-209 insulin receptor substrate 1 Rattus norvegicus 23-27 17593346-0 2007 Dilinoleoyl-phosphatidic acid mediates reduced IRS-1 tyrosine phosphorylation in rat skeletal muscle cells and mouse muscle. Tyrosine 53-61 insulin receptor substrate 1 Rattus norvegicus 47-52 17072757-7 2007 Instead, dexamethasone-induced insulin resistance may be mediated via reduced cellular content of IRS-1 accompanied by parallel reduction in tyrosine phosphorylation in IRS-1. Tyrosine 141-149 insulin receptor substrate 1 Rattus norvegicus 169-174 17288791-14 2006 IRS-1 was positive and located in the cytoplasm of the gastrocnemius cells in both the control and 30% groups; IRS-1 Tyr phosphorylation was positive in the control group and sporadic positive in the 30% group. Tyrosine 117-120 insulin receptor substrate 1 Rattus norvegicus 111-116 17288791-17 2006 Spearman correlation analysis showed that IgIRI was significantly negatively correlated with IRS-1 Tyr phosphorylation (r = -0.957, P < 0.01), and significantly positively correlated with IRS-1 Ser(307) phosphorylation (r = -0.955, P < 0.01). Tyrosine 99-102 insulin receptor substrate 1 Rattus norvegicus 93-98 17288791-18 2006 CONCLUSION: Under the status of sepsis the IRS-1 content in the skeletal muscle cells is unchanged, the level of IRS-1 Tyr phosphorylation level is decreased, and the IRS-1 Ser phosphorylation is increased. Tyrosine 119-122 insulin receptor substrate 1 Rattus norvegicus 113-118 17288791-18 2006 CONCLUSION: Under the status of sepsis the IRS-1 content in the skeletal muscle cells is unchanged, the level of IRS-1 Tyr phosphorylation level is decreased, and the IRS-1 Ser phosphorylation is increased. Tyrosine 119-122 insulin receptor substrate 1 Rattus norvegicus 113-118 17003331-5 2006 Investigation of insulin signaling revealed that bradykinin enhanced insulin receptor substrate-1 (IRS-1) Tyr phosphorylation, Akt/protein kinase B phosphorylation, and GLUT4 translocation. Tyrosine 106-109 insulin receptor substrate 1 Rattus norvegicus 99-104 16253642-6 2005 Insulin-induced insulin receptor substrate 1 tyrosine and protein kinase B serine phosphorylation were significantly reduced in the liver and muscle of fatty animals compared with their lean littermates. Tyrosine 45-53 insulin receptor substrate 1 Rattus norvegicus 16-44 17121043-5 2006 RESULTS: The protein expression of IRS-1 and the tyrosine phosphorylation levels of InsR and IRS-1 increased significantly in model rats treated with HLJD, compared with those in the untreated model rats. Tyrosine 49-57 insulin receptor substrate 1 Rattus norvegicus 93-98 17121043-6 2006 CONCLUSION: HLJD could increase the tyrosine phosphorylation levels of InsR and IRS-1 in adipose tissue in IR rats, which maybe one of its mechanisms in lowering blood glucose and improving insulin sensitivity of the target tissues. Tyrosine 36-44 insulin receptor substrate 1 Rattus norvegicus 80-85 16478771-6 2006 In vivo insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation (50%) and IRS-1-associated phosphatidylinositol-3" kinase (79%) relative to fasting plasma insulin levels were significantly elevated (P < 0.05) in plantaris muscles of GSK-3 inhibitor-treated animals. Tyrosine 45-53 insulin receptor substrate 1 Rattus norvegicus 8-36 16478771-6 2006 In vivo insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation (50%) and IRS-1-associated phosphatidylinositol-3" kinase (79%) relative to fasting plasma insulin levels were significantly elevated (P < 0.05) in plantaris muscles of GSK-3 inhibitor-treated animals. Tyrosine 45-53 insulin receptor substrate 1 Rattus norvegicus 38-43 16341686-8 2006 Although insulin receptor protein level and phosphorylation were unaltered by resistin, production of IRS-1, but not IRS-2, was downregulated and a decreased tyrosine phosphorylation of IRS-1 was detected. Tyrosine 158-166 insulin receptor substrate 1 Rattus norvegicus 186-191 16896943-6 2006 Although pSer307-IRS1 showed decreased insulin-induced tyrosine phosphorylation and interaction with phosphatidylinositol 3-kinase (PI3K) in response to insulin, pSer632-IRS1 molecules were normally tyrosine-phosphorylated and exhibited typical associated PI3K activity. Tyrosine 55-63 insulin receptor substrate 1 Rattus norvegicus 17-21 16896943-6 2006 Although pSer307-IRS1 showed decreased insulin-induced tyrosine phosphorylation and interaction with phosphatidylinositol 3-kinase (PI3K) in response to insulin, pSer632-IRS1 molecules were normally tyrosine-phosphorylated and exhibited typical associated PI3K activity. Tyrosine 199-207 insulin receptor substrate 1 Rattus norvegicus 17-21 16896943-6 2006 Although pSer307-IRS1 showed decreased insulin-induced tyrosine phosphorylation and interaction with phosphatidylinositol 3-kinase (PI3K) in response to insulin, pSer632-IRS1 molecules were normally tyrosine-phosphorylated and exhibited typical associated PI3K activity. Tyrosine 199-207 insulin receptor substrate 1 Rattus norvegicus 170-174 16729893-4 2006 Cellular insulin receptor-beta levels and tyrosine phosphorylation in IRS-1 were significantly reduced, while serine phosphorylation in IRS-1 was significantly increased in these cells, when compared to the insulin-stimulated control. Tyrosine 42-50 insulin receptor substrate 1 Rattus norvegicus 70-75 16267404-2 2005 Tyrosine phosphorylation of the insulin receptor and insulin receptor substrate 1 (IRS-1) was much lower in SK-N-BE(2) cells than in PC12 cells when the cells were treated with insulin. Tyrosine 0-8 insulin receptor substrate 1 Rattus norvegicus 83-88 15936776-9 2005 This diabetes-related suppression of skeletal muscle glucose utilization was associated with a decrease in insulin"s ability to promote the phosphorylation of tyrosine residues of insulin receptor substrate-1 (IRS-1). Tyrosine 159-167 insulin receptor substrate 1 Rattus norvegicus 180-208 15936776-9 2005 This diabetes-related suppression of skeletal muscle glucose utilization was associated with a decrease in insulin"s ability to promote the phosphorylation of tyrosine residues of insulin receptor substrate-1 (IRS-1). Tyrosine 159-167 insulin receptor substrate 1 Rattus norvegicus 210-215 15715932-11 2005 Insulin-induced tyrosine phosphorylation of the IR beta-subunit and insulin receptor substrate-1 (IRS-1) were increased in the muscle, but not in the liver of APS-treated TIIDM rats. Tyrosine 16-24 insulin receptor substrate 1 Rattus norvegicus 98-103 15921682-4 2005 Mitogen-activated protein (MAP) kinases and Akt activities, and phosphorylation of insulin receptor substrate-1 (IRS-1) at the serine and tyrosine residues were measured by immunoprecipitation and immunoblotting. Tyrosine 138-146 insulin receptor substrate 1 Rattus norvegicus 113-118 15657091-6 2005 Importantly, there were significant reductions (approximately 30-50%) in insulin stimulation of tyrosine phosphorylation of the insulin receptor beta-subunit and insulin receptor substrate-1 (IRS-1), IRS-1 associated with the p85 subunit of phosphatidylinositol 3-kinase, Akt Ser473 phosphorylation, and Ser9 phosphorylation of glycogen synthase kinase-3beta in epitrochlearis and soleus muscles of TG(mREN2)27 rats. Tyrosine 96-104 insulin receptor substrate 1 Rattus norvegicus 192-197 15657091-6 2005 Importantly, there were significant reductions (approximately 30-50%) in insulin stimulation of tyrosine phosphorylation of the insulin receptor beta-subunit and insulin receptor substrate-1 (IRS-1), IRS-1 associated with the p85 subunit of phosphatidylinositol 3-kinase, Akt Ser473 phosphorylation, and Ser9 phosphorylation of glycogen synthase kinase-3beta in epitrochlearis and soleus muscles of TG(mREN2)27 rats. Tyrosine 96-104 insulin receptor substrate 1 Rattus norvegicus 200-205 15787606-6 2005 Increased IRS1 Ser-307 phosphorylation and concomitant decreased insulin signalling as measured by insulin-stimulated IRS1 tyrosine phosphorylation and Akt threonine phosphorylation were observed in adipose tissues of Zucker obese rats compared with lean control rats. Tyrosine 123-131 insulin receptor substrate 1 Rattus norvegicus 10-14 15787606-6 2005 Increased IRS1 Ser-307 phosphorylation and concomitant decreased insulin signalling as measured by insulin-stimulated IRS1 tyrosine phosphorylation and Akt threonine phosphorylation were observed in adipose tissues of Zucker obese rats compared with lean control rats. Tyrosine 123-131 insulin receptor substrate 1 Rattus norvegicus 118-122 15718410-8 2005 However, the protein expression and functionality of tyrosine phosphorylation of insulin receptor and IRS-1, IRS-1 associated with the p85 regulatory subunit of phosphatidylinositol 3-kinase, and Ser473 phosphorylation of Akt were not altered by exercise training. Tyrosine 53-61 insulin receptor substrate 1 Rattus norvegicus 102-107 15914920-3 2005 Here we show that an amino acid unbalanced diet causes a reduction in serine phosphorylation as well as an elevation in insulin-induced tyrosine phosphorylation of IRS-1 in rat muscle. Tyrosine 136-144 insulin receptor substrate 1 Rattus norvegicus 164-169 15550510-6 2005 However, insulin-induced tyrosine phosphorylation of ERK was significantly increased (60%, P < 0.05) in adipose tissue of IRS-1AS-treated rats. Tyrosine 25-33 insulin receptor substrate 1 Rattus norvegicus 125-130 15240096-0 2004 Reduction of insulin-stimulated glucose uptake by peroxynitrite is concurrent with tyrosine nitration of insulin receptor substrate-1. Tyrosine 83-91 insulin receptor substrate 1 Rattus norvegicus 105-133 16301821-5 2005 This was followed by the inhibition of insulin-stimulated IRbeta tyrosine phosphorylation that consequently resulted inhibition of insulin receptor substrate 1 (IRS 1) and IRS 1 associated phosphatidylinositol-3 kinase (PI3 Kinase), phosphoinositide dependent kinase-1 (PDK 1) phosphorylation. Tyrosine 65-73 insulin receptor substrate 1 Rattus norvegicus 172-177 15841260-8 2004 Additionally, the increased tyrosine phosphorylation levels of IR-beta and IRS-1 were significantly inhibited in insulin combined with GJG treated diabetes. Tyrosine 28-36 insulin receptor substrate 1 Rattus norvegicus 75-80 15590973-5 2004 Higher basal levels of tyrosine phosphorylation were found in classic transducers of insulin cell signaling (IRS1, IRS2 and SHC). Tyrosine 23-31 insulin receptor substrate 1 Rattus norvegicus 109-113 15297437-8 2004 In contrast, insulin-induced tyrosine phosphorylation of IRS-1/2 and association between IRS-1/2 and PI3K were dramatically reduced after hemorrhage. Tyrosine 29-37 insulin receptor substrate 1 Rattus norvegicus 57-64 15297437-10 2004 Our data provide the first evidence that compromised IRS-1/2 tyrosine phosphorylation and their association with PI3K contribute to hemorrhage-induced acute hepatic insulin resistance. Tyrosine 61-69 insulin receptor substrate 1 Rattus norvegicus 53-60 15302844-5 2004 Insulin-stimulated tyrosine phosphorylation of insulin receptor and IRS-1 in SHR was decreased to 55% (P<0.01) and 40% (P<0.01) of the levels in Wistar-Kyoto rats (WKY), respectively. Tyrosine 19-27 insulin receptor substrate 1 Rattus norvegicus 68-73 15302844-9 2004 Serine-phosphorylated IRS-1 that was immunoprecipitated from the aorta of SHR was capable of inhibiting in vitro tyrosine phosphorylation by recombinant insulin receptor compared with WKY-derived IRS-1. Tyrosine 113-121 insulin receptor substrate 1 Rattus norvegicus 22-27 15255933-6 2004 Upon IR activation, tyrosine phosphorylation of IRS-1 was detected. Tyrosine 20-28 insulin receptor substrate 1 Rattus norvegicus 48-53 15240146-4 2004 In addition, our data show an impairment of insulin activation of IR and IRS-1 tyrosine phosphorylation in septic rats and, consistent with the reduction of IRS-1 serine phosphorylation observed in septic animals pretreated with aspirin, there was an increase in IRS-1 protein levels and tyrosine phosphorylation in muscle and WAT. Tyrosine 79-87 insulin receptor substrate 1 Rattus norvegicus 73-78 16301821-5 2005 This was followed by the inhibition of insulin-stimulated IRbeta tyrosine phosphorylation that consequently resulted inhibition of insulin receptor substrate 1 (IRS 1) and IRS 1 associated phosphatidylinositol-3 kinase (PI3 Kinase), phosphoinositide dependent kinase-1 (PDK 1) phosphorylation. Tyrosine 65-73 insulin receptor substrate 1 Rattus norvegicus 131-159 16301821-5 2005 This was followed by the inhibition of insulin-stimulated IRbeta tyrosine phosphorylation that consequently resulted inhibition of insulin receptor substrate 1 (IRS 1) and IRS 1 associated phosphatidylinositol-3 kinase (PI3 Kinase), phosphoinositide dependent kinase-1 (PDK 1) phosphorylation. Tyrosine 65-73 insulin receptor substrate 1 Rattus norvegicus 161-166 15258132-6 2004 Insulin-stimulated tyrosine phosphorylation of insulin receptor substrate (IRS)-1 was reduced by levodopa-carbidopa, although Akt phosphorylation was unaffected by levodopa-carbidopa. Tyrosine 19-27 insulin receptor substrate 1 Rattus norvegicus 47-81 15258132-7 2004 A single in vivo dose of levodopa-carbidopa increased skeletal muscle cAMP concentrations, diminished glycogen synthase activity, and reduced tyrosine phosphorylation of IRS-1. Tyrosine 142-150 insulin receptor substrate 1 Rattus norvegicus 170-175 15501480-5 2004 On the other hand, insulin-induced IRS-1 tyrosine phosphorylation was increased in both tissues while IRS-2 tyrosyl phosphorylation was increased in liver of DHEA treated group. Tyrosine 41-49 insulin receptor substrate 1 Rattus norvegicus 35-40 15326568-7 2004 Insulin resistance in rats induced by excess fructose was associated with the impaired insulin receptor (IR), tyrosine autophosphorylation, and insulin receptor substrate (IRS)-1 protein content in addition to the significant decrease in IRS-1 tyrosine phosphorylation in soleus muscle. Tyrosine 244-252 insulin receptor substrate 1 Rattus norvegicus 238-243 15240096-6 2004 Although SIN-1 did not induce Ser307 phosphorylation of IRS-1, tyrosine nitration of IRS-1 was detected in SIN-1-treated-Rat1 fibroblasts expressing human insulin receptors. Tyrosine 63-71 insulin receptor substrate 1 Rattus norvegicus 85-90 15240096-7 2004 Mass spectrometry showed that peroxynitrite induced at least four nitrated tyrosine residues in rat IRS-1, including Tyr939, which is critical for association of IRS-1 with the p85 subunit of PI-3 kinase. Tyrosine 75-83 insulin receptor substrate 1 Rattus norvegicus 100-105 15134463-3 2004 A recombinant IRS-1 fragment (rIRS-1(449)(-)(664)) containing major tyrosine motifs for interaction with phosphatidylinositol (PI) 3-kinase strongly associated to the p85alpha subunit of PI 3-kinase after Tyr phosphorylation by the insulin receptor. Tyrosine 68-76 insulin receptor substrate 1 Rattus norvegicus 14-19 15134463-3 2004 A recombinant IRS-1 fragment (rIRS-1(449)(-)(664)) containing major tyrosine motifs for interaction with phosphatidylinositol (PI) 3-kinase strongly associated to the p85alpha subunit of PI 3-kinase after Tyr phosphorylation by the insulin receptor. Tyrosine 205-208 insulin receptor substrate 1 Rattus norvegicus 14-19 14764603-8 2004 Consequently, TNF-alpha, through activation of p38 MAPK and IKK, produces serine phosphorylation of IR and IRS-1, impairing its tyrosine phosphorylation by insulin and the corresponding activation of phosphatidylinositol 3-kinase and Akt, leading to insulin resistance on glucose uptake and GLUT4 translocation. Tyrosine 128-136 insulin receptor substrate 1 Rattus norvegicus 107-112 15068962-5 2004 Immunoprecipitation studies demonstrated that IGF-I stimulation resulted in tyrosine phosphorylation of IRS-1, IRS-2, and Shc. Tyrosine 76-84 insulin receptor substrate 1 Rattus norvegicus 104-109 14670806-8 2004 Compared with NS ats, LS ats showed reduced (P < 0.01) basal and insulin-stimulated tyrosine phosphorylation of IRS-1 in skeletal muscle and IRS-2 in live, whereas HS ats showed enhanced basal tyrosine phosphorylation of IRS-1 in skeletal muscle (P < 0.05) and of IRS-2 in live. Tyrosine 87-95 insulin receptor substrate 1 Rattus norvegicus 115-120 14670806-8 2004 Compared with NS ats, LS ats showed reduced (P < 0.01) basal and insulin-stimulated tyrosine phosphorylation of IRS-1 in skeletal muscle and IRS-2 in live, whereas HS ats showed enhanced basal tyrosine phosphorylation of IRS-1 in skeletal muscle (P < 0.05) and of IRS-2 in live. Tyrosine 196-204 insulin receptor substrate 1 Rattus norvegicus 115-120 15072556-5 2004 In contrast, PF decreased the amount of IRS-1 and markedly increased phosphorylation of IRS-1 tyrosine residues after insulin injection. Tyrosine 94-102 insulin receptor substrate 1 Rattus norvegicus 88-93 15072556-8 2004 The serine dephosphorylation followed by up-regulation of insulin-dependent IRS-1 tyrosine phosphorylation in skeletal muscle of PF rats in vivo is similar to a phenomenon observed in cultured cells under restriction of amino acids in the medium. Tyrosine 82-90 insulin receptor substrate 1 Rattus norvegicus 76-81 12957877-9 2003 The defects appear to be at the level of PI3-kinase activation due to impaired insulin-induced IRS-1 tyrosine phosphorylation because of increased association of active Rho kinase with the IRS-1 leading to increased IRS-1 serine phosphorylation, which interrupts with downstream insulin signaling. Tyrosine 101-109 insulin receptor substrate 1 Rattus norvegicus 95-100 15002064-7 2004 However, the muscular insulin-stimulated IR-beta and IRS-1 tyrosine phosphorylation levels and IRS-1 associated with PI 3-kinase in HFD-fed rats were only 70 +/- 9 %, 76 +/- 5 %, and 72 +/- 6 % of controls (p < 0.05), respectively, and these decreases were significantly improved by CE treatment. Tyrosine 59-67 insulin receptor substrate 1 Rattus norvegicus 53-58 12954597-10 2003 The insulin-induced increases in tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and the binding of PI 3-kinase to IRS-1 were decreased approximately 60% in epitrochlearis muscles exposed to glucosamine. Tyrosine 33-41 insulin receptor substrate 1 Rattus norvegicus 61-95 14625128-7 2003 However, the skeletal muscle insulin-stimulated IR-beta and the IRS-1 tyrosine phosphorylation levels in C300 rats were 18 and 33% higher, respectively, added to 41% higher IRS-1/PI 3-kinase association. Tyrosine 70-78 insulin receptor substrate 1 Rattus norvegicus 64-69 13679237-11 2003 The increased tyrosine phosphorylation level of IRbeta, IRS-1, and IRS-1 associated with PI 3-kinase were significantly inhibited in KJT treated diabetes. Tyrosine 14-22 insulin receptor substrate 1 Rattus norvegicus 56-61 13679237-11 2003 The increased tyrosine phosphorylation level of IRbeta, IRS-1, and IRS-1 associated with PI 3-kinase were significantly inhibited in KJT treated diabetes. Tyrosine 14-22 insulin receptor substrate 1 Rattus norvegicus 67-72 14556646-5 2004 We observed increased IRS1 S307 phosphorylation and concomitant decrease in insulin signalling as measured by insulin-stimulated IRS1 tyrosine phosphorylation, and Akt threonine phosphorylation in adipose tissues of Zucker obese rats compared with lean control rats. Tyrosine 134-142 insulin receptor substrate 1 Rattus norvegicus 22-26 14556646-5 2004 We observed increased IRS1 S307 phosphorylation and concomitant decrease in insulin signalling as measured by insulin-stimulated IRS1 tyrosine phosphorylation, and Akt threonine phosphorylation in adipose tissues of Zucker obese rats compared with lean control rats. Tyrosine 134-142 insulin receptor substrate 1 Rattus norvegicus 129-133 14525909-6 2004 These events are accompanied by a decrease in insulin-stimulated insulin receptor/ insulin receptor substrate (IRS)-1 tyrosine phosphorylation and an increase in the IRS-2/phosphatidylinositol 3-kinase/Akt/Foxo1 pathway. Tyrosine 118-126 insulin receptor substrate 1 Rattus norvegicus 83-117 14571618-1 2003 OBJECTIVE: To investigate the effect of Bushen Tongmai recipe (BSTMR) on the tyrosine phosphorylation of insulin receptor (InsR) and insulin receptor substrate-1 (IRS-1) after insulin stimulation in muscle and fat tissues of insulin resistant (IR) rats induced by high-fat forage. Tyrosine 77-85 insulin receptor substrate 1 Rattus norvegicus 163-168 12674509-3 2003 Upon stimulation of JAK2 tyrosine phosphorylation, leptin induced JAK2 co-immunoprecipitation with STAT3, STAT5b, IRS-1 and IRS-2. Tyrosine 25-33 insulin receptor substrate 1 Rattus norvegicus 114-119 12686100-3 2003 Substrates of SSAO such as benzylamine or tyramine in combination with vanadate potently stimulate tyrosine phosphorylation of both insulin-receptor substrates 1 (IRS-1) and 3 (IRS-3) and phosphatidylinositol 3-kinase (PI 3-kinase) activity in adipose cells, which occurs in the presence of a weak stimulation of insulin-receptor kinase. Tyrosine 99-107 insulin receptor substrate 1 Rattus norvegicus 163-175 12538627-3 2003 Upon JAK2 activation, tyrosine phosphorylation of signal transducer and activator of transcription-1 (STAT-1), STAT-5b, insulin receptor substrate-1 (IRS-1), and Src homology and collagen homology (Shc) were detected. Tyrosine 22-30 insulin receptor substrate 1 Rattus norvegicus 120-148 12538627-3 2003 Upon JAK2 activation, tyrosine phosphorylation of signal transducer and activator of transcription-1 (STAT-1), STAT-5b, insulin receptor substrate-1 (IRS-1), and Src homology and collagen homology (Shc) were detected. Tyrosine 22-30 insulin receptor substrate 1 Rattus norvegicus 150-155 12538627-4 2003 In addition, LH induced IRS-1/phosphoinositol 3-kinase and Shc /growth factor receptor-binding protein 2 (Grb2) associations and downstream AKT (protein kinase B, homologous to v-AKT) serine phosphorylation and ERK tyrosine phosphorylation, respectively. Tyrosine 215-223 insulin receptor substrate 1 Rattus norvegicus 24-29 12627878-9 2003 However, tyrosine phosphorylation of IRS-1 in the soleus muscle of FFR was significantly reduced to 80% (p<0.001) of that in controls. Tyrosine 9-17 insulin receptor substrate 1 Rattus norvegicus 37-42 12006582-6 2002 Increases in intracellular C18:2 CoA and DAG concentration were associated with protein kinase C (PKC)-theta activation and a reduction in both insulin-stimulated IRS-1 tyrosine phosphorylation and IRS-1 associated PI3-kinase activity, which were associated with an increase in IRS-1 Ser(307) phosphorylation. Tyrosine 169-177 insulin receptor substrate 1 Rattus norvegicus 163-168 12837295-3 2003 TGF-beta 1 affected IGF-I-stimulated insulin receptor substrate 1 (IRS-1) tyrosine phosphorylation and its association with Grb2 protein. Tyrosine 74-82 insulin receptor substrate 1 Rattus norvegicus 37-65 12837295-3 2003 TGF-beta 1 affected IGF-I-stimulated insulin receptor substrate 1 (IRS-1) tyrosine phosphorylation and its association with Grb2 protein. Tyrosine 74-82 insulin receptor substrate 1 Rattus norvegicus 67-72 12627878-7 2003 Insulin-induced tyrosine phosphorylation of insulin receptor beta subunit (IRbeta) and insulin receptor substrate-1 (IRS-1) and tyrosine/threonine phosphorylation of p44/42 MAPK (ERK-1/2) were evaluated. Tyrosine 16-24 insulin receptor substrate 1 Rattus norvegicus 117-122 12674509-4 2003 This phenomenon parallels the leptin-induced tyrosine phosphorylation of STAT3, STAT5b, IRS-1 and IRS-2. Tyrosine 45-53 insulin receptor substrate 1 Rattus norvegicus 88-93 12153400-4 2002 VEGF augmented tyrosine phosphorylation of IRS-1 in kidney epithelial cells and rat heart endothelial cells in a time-dependent manner. Tyrosine 15-23 insulin receptor substrate 1 Rattus norvegicus 43-48 12031952-2 2002 Overexpression of an NH(2)-terminal fragment of IRS-1 that contains the pleckstrin homology and phosphotyrosine binding domains (insulin receptor substrate-1 NH(2)-terminal fragment [IRS-1N]) inhibited insulin-induced tyrosine phosphorylation of IRS-1 as well as the association of IRS-1 with phosphatidylinositol (PI) 3-kinase activity, whereas the tyrosine phosphorylation of IRS-2 and its association with PI 3-kinase activity were slightly enhanced. Tyrosine 103-111 insulin receptor substrate 1 Rattus norvegicus 48-53 12383882-7 2002 In lymphocytes obtained from control rats, the tyrosine phosphorylation of IRS-1 was time-dependent on insulin. Tyrosine 47-55 insulin receptor substrate 1 Rattus norvegicus 75-80 12383882-8 2002 In cells from diabetic rats, the basal tyrosine phosphorylation of IRS-1 was higher than that of control rats, however, there was no further phosphorylation after insulin addition. Tyrosine 39-47 insulin receptor substrate 1 Rattus norvegicus 67-72 12006582-8 2002 This in turn leads to decreased IRS-1 tyrosine phosphorylation and decreased activation of IRS-1-associated PI3-kinase activity resulting in decreased insulin-stimulated glucose transport activity. Tyrosine 38-46 insulin receptor substrate 1 Rattus norvegicus 32-37 12520087-6 2002 In addition, increased tyrosine phosphorylation of the SHB SH2 domain-adaptor protein and its association with IRS-2, IRS-1 and focal adhesion kinase was observed in these cells. Tyrosine 23-31 insulin receptor substrate 1 Rattus norvegicus 118-123 12031952-2 2002 Overexpression of an NH(2)-terminal fragment of IRS-1 that contains the pleckstrin homology and phosphotyrosine binding domains (insulin receptor substrate-1 NH(2)-terminal fragment [IRS-1N]) inhibited insulin-induced tyrosine phosphorylation of IRS-1 as well as the association of IRS-1 with phosphatidylinositol (PI) 3-kinase activity, whereas the tyrosine phosphorylation of IRS-2 and its association with PI 3-kinase activity were slightly enhanced. Tyrosine 218-226 insulin receptor substrate 1 Rattus norvegicus 48-53 12031952-2 2002 Overexpression of an NH(2)-terminal fragment of IRS-1 that contains the pleckstrin homology and phosphotyrosine binding domains (insulin receptor substrate-1 NH(2)-terminal fragment [IRS-1N]) inhibited insulin-induced tyrosine phosphorylation of IRS-1 as well as the association of IRS-1 with phosphatidylinositol (PI) 3-kinase activity, whereas the tyrosine phosphorylation of IRS-2 and its association with PI 3-kinase activity were slightly enhanced. Tyrosine 218-226 insulin receptor substrate 1 Rattus norvegicus 129-157 12031952-3 2002 The equivalent fragment of IRS-2 (IRS-2N) prevented insulin-induced tyrosine phosphorylation of both IRS-1 and IRS-2, although that of IRS-1 was inhibited more efficiently. Tyrosine 68-76 insulin receptor substrate 1 Rattus norvegicus 101-106 12031952-4 2002 The insulin-induced increases in the abundance of SREBP-1c and glucokinase mRNAs, both of which were sensitive to a dominant-negative mutant of PI 3-kinase, were blocked in cells in which the insulin-induced tyrosine phosphorylation of IRS-1 was inhibited by IRS-1N or IRS-2N. Tyrosine 208-216 insulin receptor substrate 1 Rattus norvegicus 236-241 12031952-5 2002 A dominant-negative mutant of Akt enhanced insulin-induced tyrosine phosphorylation of IRS-1 (but not that of IRS-2) and its association with PI 3-kinase activity, suggesting that Akt contributes to negative feedback regulation of IRS-1. Tyrosine 59-67 insulin receptor substrate 1 Rattus norvegicus 87-92 12031952-5 2002 A dominant-negative mutant of Akt enhanced insulin-induced tyrosine phosphorylation of IRS-1 (but not that of IRS-2) and its association with PI 3-kinase activity, suggesting that Akt contributes to negative feedback regulation of IRS-1. Tyrosine 59-67 insulin receptor substrate 1 Rattus norvegicus 231-236 12166618-4 2002 The results demonstrated that insulin-induced IRS-1/PI 3-kinase association has a close correlation with IRS-1 tyrosine phosphorylation levels, but insulin-induced IRS-1/SHP2 association showed a modulation that did not parallel IRS-1 phosphorylation, with a tissue-specific regulation in aging. Tyrosine 111-119 insulin receptor substrate 1 Rattus norvegicus 46-51 12166618-4 2002 The results demonstrated that insulin-induced IRS-1/PI 3-kinase association has a close correlation with IRS-1 tyrosine phosphorylation levels, but insulin-induced IRS-1/SHP2 association showed a modulation that did not parallel IRS-1 phosphorylation, with a tissue-specific regulation in aging. Tyrosine 111-119 insulin receptor substrate 1 Rattus norvegicus 105-110 12166618-4 2002 The results demonstrated that insulin-induced IRS-1/PI 3-kinase association has a close correlation with IRS-1 tyrosine phosphorylation levels, but insulin-induced IRS-1/SHP2 association showed a modulation that did not parallel IRS-1 phosphorylation, with a tissue-specific regulation in aging. Tyrosine 111-119 insulin receptor substrate 1 Rattus norvegicus 105-110 12166618-4 2002 The results demonstrated that insulin-induced IRS-1/PI 3-kinase association has a close correlation with IRS-1 tyrosine phosphorylation levels, but insulin-induced IRS-1/SHP2 association showed a modulation that did not parallel IRS-1 phosphorylation, with a tissue-specific regulation in aging. Tyrosine 111-119 insulin receptor substrate 1 Rattus norvegicus 105-110 11976270-4 2002 Immunoprecipitation and immunoblotting were used to detect insulin-mediated tyrosine phosphorylation of both IR-beta and insulin receptor substrate (IRS)-1, and insulin-stimulated binding of IRS-1 to p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3-K) in the extracted muscle. Tyrosine 76-84 insulin receptor substrate 1 Rattus norvegicus 121-155 11832371-3 2002 In contrast, in leg muscle, IR density, as determined by Western blotting, was not affected, whereas IR and IRS-1 tyrosine phosphorylation in response to insulin treatment was restored in animals fed with n-3 PUFA to normal; in n-6 PUFA, the phosphorylation was depressed, as evidenced by Western blot analysis using specific antibodies. Tyrosine 114-122 insulin receptor substrate 1 Rattus norvegicus 108-113 11739394-4 2002 Hypertension (in spontaneous hypertensive rats) or expression of an active RhoA(V14) up-regulates Rho kinase activity and increases ROK-alpha/IRS-1 association resulting in IRS-1 serine phosphorylation that leads to inhibition of both insulin-induced IRS-1 tyrosine phosphorylation and phosphatidylinositol 3-kinase (PI3-kinase) activation. Tyrosine 257-265 insulin receptor substrate 1 Rattus norvegicus 173-178 11739394-4 2002 Hypertension (in spontaneous hypertensive rats) or expression of an active RhoA(V14) up-regulates Rho kinase activity and increases ROK-alpha/IRS-1 association resulting in IRS-1 serine phosphorylation that leads to inhibition of both insulin-induced IRS-1 tyrosine phosphorylation and phosphatidylinositol 3-kinase (PI3-kinase) activation. Tyrosine 257-265 insulin receptor substrate 1 Rattus norvegicus 173-178 11707432-4 2002 Pharmacological depletion of GM3 in adipocytes by an inhibitor of glucosylceramide synthase prevented the TNF-alpha-induced defect in insulin-dependent tyrosine phosphorylation of IRS-1 and also counteracted the TNF-alpha-induced serine phosphorylation of IRS-1. Tyrosine 152-160 insulin receptor substrate 1 Rattus norvegicus 180-185 11785657-9 2001 In addition, we demonstrated that PMA inhibited the insulin-induced tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1). Tyrosine 68-76 insulin receptor substrate 1 Rattus norvegicus 126-131 11724574-6 2001 Here we describe that stimulation of glucose transport in isolated rat adipocytes by a different stimulus, the sulfonylurea glimepiride, is also based on IRS-1/2 tyrosine phosphorylation and downstream insulin-mimetic signaling involving activation of the NRTK, pp59(Lyn), and pp125(Fak), as well as tyrosine phosphoryation of the DIGs component caveolin. Tyrosine 162-170 insulin receptor substrate 1 Rattus norvegicus 154-159 11723053-2 2001 The levels of insulin-stimulated tyrosine phosphorylation of the insulin receptor beta-subunit, insulin receptor substrate (IRS)-2, and p52(Shc) were increased in diabetic compared with control heart, whereas tyrosine phosphorylation of IRS-1 was unchanged. Tyrosine 33-41 insulin receptor substrate 1 Rattus norvegicus 237-242 11574414-15 2001 In conclusion, acutely elevated FFA levels 1) induced a significant reduction in tracer-determined GDR paralleled by impaired tyrosine phosphorylation of IRS-1 and reduced IRS-1-associated PI 3-kinase activity and 2) induced a significant reduction in FAT/CD36 total protein. Tyrosine 126-134 insulin receptor substrate 1 Rattus norvegicus 154-159 11563846-5 2001 Insulin induced rapid tyrosine-phosphorylation of the IR and IRS-1 and caused a 2.8-fold increase of IRS-1-bound PI3K. Tyrosine 22-30 insulin receptor substrate 1 Rattus norvegicus 61-66 11564986-8 2001 PI3-kinase activity, IRS-1-associated tyrosine phosphorylation and p85 subunit of PI3-kinase in VSMC from WKY rats decreased in response to treatment with Ang II and returned to control levels upon co-treatment with U0126. Tyrosine 38-46 insulin receptor substrate 1 Rattus norvegicus 21-26 11564986-9 2001 Basal levels of PI3-kinase activity, IRS-1-associated tyrosine phosphorylation, and p85 subunit of PI3-kinase were significantly lower in VSMC from SHR than in cells from WKY rats. Tyrosine 54-62 insulin receptor substrate 1 Rattus norvegicus 37-42 11564986-10 2001 U0126 treatment of VSMC from SHR significantly increased levels of PI3-kinase activity, IRS-1-associated tyrosine phosphorylation, and p85 subunit of PI3-kinase. Tyrosine 105-113 insulin receptor substrate 1 Rattus norvegicus 88-93 11463579-6 2001 A 10 min exposure to homocysteine thiolactone (50 microM) resulted in a significant inhibition of insulin-stimulated tyrosine phosphorylation of the insulin receptor beta-subunit and its substrates IRS-1 and p60-70, as well as their association with the p85 regulatory subunit of phosphatidylinositol 3-kinase. Tyrosine 117-125 insulin receptor substrate 1 Rattus norvegicus 198-203 11724574-6 2001 Here we describe that stimulation of glucose transport in isolated rat adipocytes by a different stimulus, the sulfonylurea glimepiride, is also based on IRS-1/2 tyrosine phosphorylation and downstream insulin-mimetic signaling involving activation of the NRTK, pp59(Lyn), and pp125(Fak), as well as tyrosine phosphoryation of the DIGs component caveolin. Tyrosine 300-308 insulin receptor substrate 1 Rattus norvegicus 154-159 10848643-4 2000 In insulin-treated rats, tyrosine-phosphorylated IR was 79% higher for CR vs. AL; tyrosine-phosphorylated IRS1 was 109% higher for CR vs. AL; IRS1-associated PI3K protein and IRS1-associated PI3K activity were unaffected by diet. Tyrosine 25-33 insulin receptor substrate 1 Rattus norvegicus 142-146 11278339-4 2001 Wortmannin, a phosphatidylinositol 3-kinase (PI3K) inhibitor, abolished the increase in the P-Ser/Thr content of IRS-1, its dissociation from the IR, and the decrease in its P-Tyr content following 60 min of insulin treatment, indicating that the Ser kinases that negatively regulate IRS-1 function are downstream effectors of PI3K. Tyrosine 176-179 insulin receptor substrate 1 Rattus norvegicus 113-118 11278339-6 2001 Overexpression of PKCzeta in Fao cells, by infection of the cells with adenovirus-based PKCzeta construct, had no effect on its own, but it accelerated the rate of insulin-stimulated dissociation of IR.IRS-1 complexes and the rate of Tyr dephosphorylation of IRS-1. Tyrosine 234-237 insulin receptor substrate 1 Rattus norvegicus 202-207 11278339-8 2001 Because the reduction in P-Tyr content of IRS-1 was accompanied by a reduced association of IRS-1 with p85, the regulatory subunit of PI3K, it suggests that this negative regulatory process induced by PKCzeta, has a built-in attenuation signal. Tyrosine 27-30 insulin receptor substrate 1 Rattus norvegicus 42-47 11279262-0 2001 Tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) by oxidant stress in cerebellar granule neurons: modulation by N-methyl-D-aspartate through calcineurin activity. Tyrosine 0-8 insulin receptor substrate 1 Rattus norvegicus 28-56 11279262-0 2001 Tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) by oxidant stress in cerebellar granule neurons: modulation by N-methyl-D-aspartate through calcineurin activity. Tyrosine 0-8 insulin receptor substrate 1 Rattus norvegicus 58-63 11279262-2 2001 Upon tyrosine phosphorylation, IRS-1 binds to signaling molecules that express Src homology 2 (SH-2) binding domains, including phosphatidylinositol 3-kinase (PI 3-kinase), phosphotyrosine phosphatase SHP-2 (Syp), Nck, Crk and Grb-2. Tyrosine 5-13 insulin receptor substrate 1 Rattus norvegicus 31-36 11279262-5 2001 In the current study, we examined the effect of H(2)O(2) on IRS-1 tyrosine phosphorylation in primary cultured rat cerebellar granule neurons. Tyrosine 66-74 insulin receptor substrate 1 Rattus norvegicus 60-65 11279262-6 2001 H(2)O(2) stimulated the rapid tyrosine phosphorylation of IRS-1 and p42/p44 MAP kinase, and induced its association with PI 3-kinase. Tyrosine 30-38 insulin receptor substrate 1 Rattus norvegicus 58-63 11279262-9 2001 Calmodulin-dependent tyrosine phosphatase activity of calcineurin was observed in vitro using both immunoprecipitated and recombinant tyrosine-phosphorylated IRS-1 as substrates. Tyrosine 21-29 insulin receptor substrate 1 Rattus norvegicus 158-163 11279262-10 2001 These data highlight the role of multiple phosphatases in the regulation of IRS-1 tyrosine phosphorylation and identify a novel functional property of calcineurin. Tyrosine 82-90 insulin receptor substrate 1 Rattus norvegicus 76-81 11121405-9 2001 Insulin-increased tyrosine phosphorylation of an immediate downstream signal transducer, insulin receptor substrate-1, and activation of the further downstream protein kinase B were inhibited. Tyrosine 18-26 insulin receptor substrate 1 Rattus norvegicus 89-117 11105093-1 2000 Insulin stimulates the tyrosine kinase activity of its receptor resulting in the tyrosine phosphorylation of pp185, which contains insulin receptor substrates IRS-1 and IRS-2. Tyrosine 23-31 insulin receptor substrate 1 Rattus norvegicus 109-114 11105093-1 2000 Insulin stimulates the tyrosine kinase activity of its receptor resulting in the tyrosine phosphorylation of pp185, which contains insulin receptor substrates IRS-1 and IRS-2. Tyrosine 23-31 insulin receptor substrate 1 Rattus norvegicus 159-164 10926841-6 2000 Benzylamine or tyramine in combination with vanadate potently stimulated the tyrosine phosphorylation of both insulin receptor substrate (IRS)-1 and IRS-3. Tyrosine 77-85 insulin receptor substrate 1 Rattus norvegicus 110-144 10926841-11 2000 SSAO oxidative activity stimulates glucose transport via the translocation of GLUT4 carriers to the cell surface, resulting from a potent tyrosine phosphorylation of IRS-1 and IRS-3 and phosphoinositide 3-kinase activation. Tyrosine 138-146 insulin receptor substrate 1 Rattus norvegicus 166-171 10924321-2 2000 Relative to non-diabetic control rats (WKY), insulin-stimulated insulin receptor (IR) autophosphorylation and insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation were significantly inhibited in GK skeletal muscles. Tyrosine 147-155 insulin receptor substrate 1 Rattus norvegicus 110-138 10924321-2 2000 Relative to non-diabetic control rats (WKY), insulin-stimulated insulin receptor (IR) autophosphorylation and insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation were significantly inhibited in GK skeletal muscles. Tyrosine 147-155 insulin receptor substrate 1 Rattus norvegicus 140-145 10924365-3 2000 The insulin-dependent tyrosine phosphorylation of IRS-1 in the internal membrane and its association with phosphatidylinositol 3 (PI3) kinase preceded MAP kinase activation. Tyrosine 22-30 insulin receptor substrate 1 Rattus norvegicus 50-55 11229432-6 2001 Insulin-stimulated percent tyrosine phosphorylation of IRS-1, normalized to the IRS-1 protein expression, was also reduced to 55% (P < .01) of control in denervated muscle. Tyrosine 27-35 insulin receptor substrate 1 Rattus norvegicus 55-60 11229432-6 2001 Insulin-stimulated percent tyrosine phosphorylation of IRS-1, normalized to the IRS-1 protein expression, was also reduced to 55% (P < .01) of control in denervated muscle. Tyrosine 27-35 insulin receptor substrate 1 Rattus norvegicus 80-85 11121098-1 2001 Short-term incubation of adult rat hepatocytes with epidermal growth factor (EGF) caused tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and IRS-2 when the cells had been submitted to primary culture from 1-18 h. Tyrosine-phosphorylated IRS-1 and IRS-2 bound to the regulatory subunit (p85) of phosphatidylinositol (PtdIns) 3-kinase, thereby activating the enzymic activity. Tyrosine 89-97 insulin receptor substrate 1 Rattus norvegicus 117-151 11121098-1 2001 Short-term incubation of adult rat hepatocytes with epidermal growth factor (EGF) caused tyrosine phosphorylation of insulin receptor substrate (IRS)-1 and IRS-2 when the cells had been submitted to primary culture from 1-18 h. Tyrosine-phosphorylated IRS-1 and IRS-2 bound to the regulatory subunit (p85) of phosphatidylinositol (PtdIns) 3-kinase, thereby activating the enzymic activity. Tyrosine 228-236 insulin receptor substrate 1 Rattus norvegicus 117-151 10848597-3 2000 Introduction by electroporation of neutralizing antibodies against pp59(Lyn) and pp125(FAK) into isolated rat adipocytes blocked IRS-1 tyrosine phosphorylation in response to PIG but not insulin. Tyrosine 135-143 insulin receptor substrate 1 Rattus norvegicus 129-134 10848643-4 2000 In insulin-treated rats, tyrosine-phosphorylated IR was 79% higher for CR vs. AL; tyrosine-phosphorylated IRS1 was 109% higher for CR vs. AL; IRS1-associated PI3K protein and IRS1-associated PI3K activity were unaffected by diet. Tyrosine 25-33 insulin receptor substrate 1 Rattus norvegicus 142-146 10848643-4 2000 In insulin-treated rats, tyrosine-phosphorylated IR was 79% higher for CR vs. AL; tyrosine-phosphorylated IRS1 was 109% higher for CR vs. AL; IRS1-associated PI3K protein and IRS1-associated PI3K activity were unaffected by diet. Tyrosine 82-90 insulin receptor substrate 1 Rattus norvegicus 106-110 10848643-4 2000 In insulin-treated rats, tyrosine-phosphorylated IR was 79% higher for CR vs. AL; tyrosine-phosphorylated IRS1 was 109% higher for CR vs. AL; IRS1-associated PI3K protein and IRS1-associated PI3K activity were unaffected by diet. Tyrosine 82-90 insulin receptor substrate 1 Rattus norvegicus 142-146 10848643-4 2000 In insulin-treated rats, tyrosine-phosphorylated IR was 79% higher for CR vs. AL; tyrosine-phosphorylated IRS1 was 109% higher for CR vs. AL; IRS1-associated PI3K protein and IRS1-associated PI3K activity were unaffected by diet. Tyrosine 82-90 insulin receptor substrate 1 Rattus norvegicus 142-146 10788447-10 2000 PMA also decreased IGF-1-induced tyrosine phosphorylation of insulin receptor substrate-1 and its association with PI3K. Tyrosine 33-41 insulin receptor substrate 1 Rattus norvegicus 61-89 10842668-5 1999 Insulin-stimulated phosphorylation of tyrosine residues on the insulin receptor and on the associated docking protein IRS-1 are reduced in skeletal muscle and liver compared to SHR, due mainly to diminished expression of insulin receptor and IRS-1 proteins. Tyrosine 38-46 insulin receptor substrate 1 Rattus norvegicus 118-123 10692429-1 2000 Protein-tyrosine phosphatases (PTPases) play a key role in maintaining the steady-state tyrosine phosphorylation of the insulin receptor (IR) and its substrate proteins such as insulin receptor substrate 1 (IRS-1). Tyrosine 8-16 insulin receptor substrate 1 Rattus norvegicus 177-205 10692429-1 2000 Protein-tyrosine phosphatases (PTPases) play a key role in maintaining the steady-state tyrosine phosphorylation of the insulin receptor (IR) and its substrate proteins such as insulin receptor substrate 1 (IRS-1). Tyrosine 8-16 insulin receptor substrate 1 Rattus norvegicus 207-212 10839189-4 2000 There was a marked impairment in the insulin stimulated tyrosine phosphorylation of IRS-1 and 2 as well as activation of PI3-kinase and PKB in cells from old and obese animals. Tyrosine 56-64 insulin receptor substrate 1 Rattus norvegicus 84-95 10842668-5 1999 Insulin-stimulated phosphorylation of tyrosine residues on the insulin receptor and on the associated docking protein IRS-1 are reduced in skeletal muscle and liver compared to SHR, due mainly to diminished expression of insulin receptor and IRS-1 proteins. Tyrosine 38-46 insulin receptor substrate 1 Rattus norvegicus 242-247 10551398-4 1999 RESULTS: Expression of insulin receptor substrate-1 (IRS-1) showed a 1.4-fold increase at protein level in the tumors (p<0.01), but the tyrosine phosphorylation of IRS-1 did not differ between the tumor and control liver. Tyrosine 139-147 insulin receptor substrate 1 Rattus norvegicus 23-51 10551398-4 1999 RESULTS: Expression of insulin receptor substrate-1 (IRS-1) showed a 1.4-fold increase at protein level in the tumors (p<0.01), but the tyrosine phosphorylation of IRS-1 did not differ between the tumor and control liver. Tyrosine 139-147 insulin receptor substrate 1 Rattus norvegicus 53-58 10535386-5 1999 Phosphatidylinositol 3-kinase (PI 3-kinase) activity associated with hepatic insulin receptor substrate-1 (IRS-1) in the insulin-stimulated condition was significantly enhanced 110% without a significant alteration in tyrosine phosphorylation of IRS-1 in the imidapril-treated group. Tyrosine 218-226 insulin receptor substrate 1 Rattus norvegicus 107-112 10535386-6 1999 In muscle, IRS-1 tyrosine phosphorylation and PI 3-kinase activity associated with IRS-1 in the insulin-stimulated condition were enhanced 70% and 20%, respectively, in the imidapril-treated group. Tyrosine 17-25 insulin receptor substrate 1 Rattus norvegicus 11-16 10535386-6 1999 In muscle, IRS-1 tyrosine phosphorylation and PI 3-kinase activity associated with IRS-1 in the insulin-stimulated condition were enhanced 70% and 20%, respectively, in the imidapril-treated group. Tyrosine 17-25 insulin receptor substrate 1 Rattus norvegicus 83-88 10449437-5 1999 Insulin-induced tyrosine phosphorylation of insulin receptor substrates 1 and 2 (IRS-1 and IRS-2) and their protein levels were decreased in the aorta of obese rats compared with lean rats. Tyrosine 16-24 insulin receptor substrate 1 Rattus norvegicus 81-86 10381377-9 1999 Insulin-induced tyrosine phosphorylation of IRS-1, IRS-1 association with the p85 subunit of PI3-kinase, and PI3-kinase activation were not affected by overexpression of SHIP2. Tyrosine 16-24 insulin receptor substrate 1 Rattus norvegicus 44-49 10320054-5 1999 Results generated in the in vivo studies indicate that, like insulin, AII stimulates tyrosine phosphorylation of the insulin receptor substrates IRS-1 and IRS-2. Tyrosine 85-93 insulin receptor substrate 1 Rattus norvegicus 145-150 10224126-7 1999 Treatment of L6 cells with insulin resulted in tyrosine phosphorylation of IRS1, increased cellular production of phosphatidylinositol 3,4,5-phosphate and a 41-fold activation in protein kinase B (PKB/Akt) activity. Tyrosine 47-55 insulin receptor substrate 1 Rattus norvegicus 75-79 10080958-5 1999 Insulin-induced tyrosine phosphorylation of IRS-1 was less in TBR than controls, but that of the IR was similar among the three groups. Tyrosine 16-24 insulin receptor substrate 1 Rattus norvegicus 44-49 10067837-3 1999 Insulin rapidly stimulated tyrosine phosphorylation of the insulin receptor, insulin receptor substrate-1 (IRS-1) and, to a lesser extent, IRS-2 in normal and diabetic myocardium. Tyrosine 27-35 insulin receptor substrate 1 Rattus norvegicus 107-112 10067837-5 1999 IRS-1 tyrosine phosphorylation also increased in STZ diabetes in spite of a decrease in IRS-1 content, resulting in a 4-fold higher ratio of phosphorylated to total IRS-1. Tyrosine 6-14 insulin receptor substrate 1 Rattus norvegicus 0-5 9886807-3 1999 In cultured cells, GH stimulates the tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1), IRS-2, and Shc. Tyrosine 37-45 insulin receptor substrate 1 Rattus norvegicus 65-93 9886807-3 1999 In cultured cells, GH stimulates the tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1), IRS-2, and Shc. Tyrosine 37-45 insulin receptor substrate 1 Rattus norvegicus 95-100 9886807-6 1999 GH increased the tyrosine phosphorylation of IRS-1, IRS-2, JAK2, and Shc proteins in the liver, heart, kidney, muscle, and adipose tissue of rats. Tyrosine 17-25 insulin receptor substrate 1 Rattus norvegicus 45-50 9837876-4 1998 Clustering of beta1-integrin also significantly potentiated stimulation of insulin receptor and IRS-1 tyrosine phosphorylation, IRS-associated PI 3-kinase activity, and Akt/PKB activation caused by submaximal concentrations of insulin. Tyrosine 102-110 insulin receptor substrate 1 Rattus norvegicus 96-101 9806898-4 1998 The five compounds elicited in rat adipocytes a significant increase in tyrosine phosphorylation of both insulin receptor substrate 1 (IRS-1) and IRS-3 and, to a minor degree, IRS-2, in IRS-1/3-associated phosphatidylinositol 3-kinase (PI 3-K) protein as well as activity, and in protein kinase B (PKB) activity as well as phosphorylation. Tyrosine 72-80 insulin receptor substrate 1 Rattus norvegicus 105-133 9806898-4 1998 The five compounds elicited in rat adipocytes a significant increase in tyrosine phosphorylation of both insulin receptor substrate 1 (IRS-1) and IRS-3 and, to a minor degree, IRS-2, in IRS-1/3-associated phosphatidylinositol 3-kinase (PI 3-K) protein as well as activity, and in protein kinase B (PKB) activity as well as phosphorylation. Tyrosine 72-80 insulin receptor substrate 1 Rattus norvegicus 135-140 10078575-7 1999 In EDL muscle, insulin-stimulated IRS-1 tyrosine phosphorylation and IRS-1-associated PI-3 kinase were not altered between GK and Wistar rats. Tyrosine 40-48 insulin receptor substrate 1 Rattus norvegicus 34-39 9892238-4 1999 The tyrosine phosphorylation levels of IRS-1 and IRS-2 were not significantly altered, however. Tyrosine 4-12 insulin receptor substrate 1 Rattus norvegicus 39-44 9792680-2 1998 We demonstrated that IRS-1 and IRS-2 are located mainly in the low density microsome (LDM) fraction and are tyrosine phosphorylated in response to insulin stimulation, leading to phosphatidylinositol (PI) 3-kinase activation. Tyrosine 108-116 insulin receptor substrate 1 Rattus norvegicus 21-26 9921276-7 1998 This association occurred when IRS-1 had the highest level of tyrosine phosphorylation and the decrease in this association was more rapid than the decrease in IRS-1 phosphorylation levels. Tyrosine 62-70 insulin receptor substrate 1 Rattus norvegicus 31-36 9495542-3 1997 APP stimulated the tyrosine phosphorylation of a number of proteins including insulin receptor substrate-1 (IRS-1). Tyrosine 19-27 insulin receptor substrate 1 Rattus norvegicus 78-106 9609114-7 1998 Using an in vivo rat liver model in which endosomal IRKs are exclusively activated has revealed that IRKs at this intracellular locus are able by themselves to promote IRS-1 tyrosine phosphorylation and induce hypoglycemia. Tyrosine 174-182 insulin receptor substrate 1 Rattus norvegicus 168-173 9609114-8 1998 Furthermore, studies with isolated rat adipocytes reveal the EN to be the principle site of insulin-stimulated IRS-1 tyrosine phosphorylation and associated PI3K activation. Tyrosine 117-125 insulin receptor substrate 1 Rattus norvegicus 111-116 9562343-6 1998 JTT-501 treatment restored appreciably the protein content and tyrosine phosphorylation level of IRS-1. Tyrosine 63-71 insulin receptor substrate 1 Rattus norvegicus 97-102 9756898-5 1998 The antiapoptotic action of NMDA was associated with an increase in the tyrosine phosphorylation of insulin receptor substrate 1 (IRS-1), an increase in the binding of the regulatory subunit of PI 3-kinase to IRS-1, and a stimulation of PI 3-kinase activity. Tyrosine 72-80 insulin receptor substrate 1 Rattus norvegicus 100-128 9692679-3 1998 Insulin treatment caused a 15-fold increase in tyrosine phosphorylation of IRS-1 in the caveolin-enriched fraction in 5 min at 37 degrees C compared with a 3-fold increase in plasma membranes and a 6-fold increases in the cytosol and endosomes. Tyrosine 47-55 insulin receptor substrate 1 Rattus norvegicus 75-80 9468304-0 1998 Regulation of insulin-stimulated tyrosine phosphorylation of Shc and IRS-1 in the muscle of rats: effect of growth hormone and epinephrine. Tyrosine 33-41 insulin receptor substrate 1 Rattus norvegicus 69-74 9421369-2 1998 The expressions of IRS-1 and IRS-2 were shown to be downregulated in both liver and muscle in fatty rats (hepatic IRS-1, 83%; hepatic IRS-2, 45%; muscle IRS-1, 60%; muscle IRS-2, 78%), resulting in decreased tyrosine phosphorylation in response to insulin stimulation. Tyrosine 208-216 insulin receptor substrate 1 Rattus norvegicus 19-24 9440478-7 1998 In addition, insulin-stimulated tyrosine phosphorylation of insulin receptor (IR) substrate-1 (IRS-1) was decreased more than 90% compared with control values, while a twofold increase in basal IRS-1 phosphorylation status was observed in diabetic GK rats. Tyrosine 32-40 insulin receptor substrate 1 Rattus norvegicus 95-100 9440478-7 1998 In addition, insulin-stimulated tyrosine phosphorylation of insulin receptor (IR) substrate-1 (IRS-1) was decreased more than 90% compared with control values, while a twofold increase in basal IRS-1 phosphorylation status was observed in diabetic GK rats. Tyrosine 32-40 insulin receptor substrate 1 Rattus norvegicus 194-199 9495542-3 1997 APP stimulated the tyrosine phosphorylation of a number of proteins including insulin receptor substrate-1 (IRS-1). Tyrosine 19-27 insulin receptor substrate 1 Rattus norvegicus 108-113 9438994-1 1997 Insulin stimulates tyrosine phosphorylation of 175-195 kDa proteins including insulin receptor substrate-1 (IRS-1) in various tissues and cell types. Tyrosine 19-27 insulin receptor substrate 1 Rattus norvegicus 78-106 9438994-1 1997 Insulin stimulates tyrosine phosphorylation of 175-195 kDa proteins including insulin receptor substrate-1 (IRS-1) in various tissues and cell types. Tyrosine 19-27 insulin receptor substrate 1 Rattus norvegicus 108-113 9415393-2 1997 Studies in adipose cells have demonstrated that insulin stimulates its receptor to phosphorylate tyrosine residues in IRS-1, leading to activation of phosphatidylinositol 3-kinase, which plays a necessary role in mediating the translocation of the insulin-responsive glucose transporter GLUT4 to the cell surface. Tyrosine 97-105 insulin receptor substrate 1 Rattus norvegicus 118-123 9368067-1 1997 Elevated serine/threonine phosphorylation of IRS-1 and IRS-2 inhibits their binding to the juxtamembrane region of the insulin receptor and impairs their ability to undergo insulin-induced tyrosine phosphorylation. Tyrosine 189-197 insulin receptor substrate 1 Rattus norvegicus 45-50 9374689-7 1997 Insulin-stimulated tyrosine phosphorylation of the insulin receptor beta-subunit and insulin receptor substrate-1 (IRS-1) in intact skeletal muscle of SHROB was reduced by 36 and 23%, respectively, compared with SHR, due primarily to 32 and 60% decreases in insulin receptor and IRS-1 protein expression, respectively. Tyrosine 19-27 insulin receptor substrate 1 Rattus norvegicus 115-120 9395231-11 1997 In accord with this observation, tyrosine-phosphorylated activation of insulin receptor substrate-1, detected by immunoprecipitation and Western immunoblot analysis in mammary tumors of WC rats from our previous study, was 3-5 times greater than in non-restricted controls (P < 0.01). Tyrosine 33-41 insulin receptor substrate 1 Rattus norvegicus 71-99 9410892-4 1997 While AII did not impair insulin-stimulated tyrosine phosphorylation of the insulin receptor (IR) beta-subunit, it decreased insulin-stimulated tyrosine phosphorylation of IRS-1 by 50%. Tyrosine 144-152 insulin receptor substrate 1 Rattus norvegicus 172-177 9368067-5 1997 Moreover, incubation of rat hepatoma Fao cells with TNFalpha, bacterial sphingomyelinase, or other Ser(P)/Thr(P)-elevating agents reduced insulin-induced Tyr phosphorylation of IRS-1 and IRS-2, markedly elevated their Ser(P)/Thr(P) levels, and significantly reduced their ability to interact with the JM region of IR. Tyrosine 154-157 insulin receptor substrate 1 Rattus norvegicus 177-182 9368067-10 1997 Such impaired interactions abolish the ability of IRS-1 and IRS-2 to undergo insulin-induced Tyr phosphorylation and further propagate the insulin receptor signal. Tyrosine 93-96 insulin receptor substrate 1 Rattus norvegicus 50-55 9374689-7 1997 Insulin-stimulated tyrosine phosphorylation of the insulin receptor beta-subunit and insulin receptor substrate-1 (IRS-1) in intact skeletal muscle of SHROB was reduced by 36 and 23%, respectively, compared with SHR, due primarily to 32 and 60% decreases in insulin receptor and IRS-1 protein expression, respectively. Tyrosine 19-27 insulin receptor substrate 1 Rattus norvegicus 279-284 9374689-9 1997 In the liver of SHROB, the effect of insulin on tyrosine phosphorylation of IRS-1 was not changed, but insulin receptor phosphorylation was decreased by 41%, compared with SHR, due to a 30% reduction in insulin receptor levels. Tyrosine 48-56 insulin receptor substrate 1 Rattus norvegicus 76-81 9291837-0 1997 Changes in tyrosine phosphorylation of insulin receptor and insulin receptor substrate-1 (IRS-1) and association of p85 of phosphatidylinositol 3-kinase with IRS-1 after feeding in rat liver in vivo. Tyrosine 11-19 insulin receptor substrate 1 Rattus norvegicus 90-95 9291837-1 1997 The binding of insulin to its receptor rapidly induces intrinsic insulin receptor tyrosine kinase activity, resulting in tyrosine phosphorylation of various cytosolic substrates, such as insulin receptor substrate-1 (IRS-1) which, in turn, associates with a p85 subunit of phosphatidylinositol 3-kinase (PI 3-kinase) followed by activation of this enzyme. Tyrosine 82-90 insulin receptor substrate 1 Rattus norvegicus 187-215 9291837-1 1997 The binding of insulin to its receptor rapidly induces intrinsic insulin receptor tyrosine kinase activity, resulting in tyrosine phosphorylation of various cytosolic substrates, such as insulin receptor substrate-1 (IRS-1) which, in turn, associates with a p85 subunit of phosphatidylinositol 3-kinase (PI 3-kinase) followed by activation of this enzyme. Tyrosine 82-90 insulin receptor substrate 1 Rattus norvegicus 217-222 9291837-5 1997 Basal tyrosine phosphorylation of IRS-1 was detectable during starvation, increased about twofold at 3 h after feeding and levels were maintained until 8 h. The content of the p85 subunit of PI 3-kinase associated with IRS-1 also increased after feeding in parallel with the changes in tyrosine phosphorylation of IRS-1. Tyrosine 6-14 insulin receptor substrate 1 Rattus norvegicus 34-39 9291837-5 1997 Basal tyrosine phosphorylation of IRS-1 was detectable during starvation, increased about twofold at 3 h after feeding and levels were maintained until 8 h. The content of the p85 subunit of PI 3-kinase associated with IRS-1 also increased after feeding in parallel with the changes in tyrosine phosphorylation of IRS-1. Tyrosine 6-14 insulin receptor substrate 1 Rattus norvegicus 219-224 9291837-5 1997 Basal tyrosine phosphorylation of IRS-1 was detectable during starvation, increased about twofold at 3 h after feeding and levels were maintained until 8 h. The content of the p85 subunit of PI 3-kinase associated with IRS-1 also increased after feeding in parallel with the changes in tyrosine phosphorylation of IRS-1. Tyrosine 6-14 insulin receptor substrate 1 Rattus norvegicus 219-224 9291837-5 1997 Basal tyrosine phosphorylation of IRS-1 was detectable during starvation, increased about twofold at 3 h after feeding and levels were maintained until 8 h. The content of the p85 subunit of PI 3-kinase associated with IRS-1 also increased after feeding in parallel with the changes in tyrosine phosphorylation of IRS-1. Tyrosine 286-294 insulin receptor substrate 1 Rattus norvegicus 34-39 9291837-5 1997 Basal tyrosine phosphorylation of IRS-1 was detectable during starvation, increased about twofold at 3 h after feeding and levels were maintained until 8 h. The content of the p85 subunit of PI 3-kinase associated with IRS-1 also increased after feeding in parallel with the changes in tyrosine phosphorylation of IRS-1. Tyrosine 286-294 insulin receptor substrate 1 Rattus norvegicus 219-224 9291837-5 1997 Basal tyrosine phosphorylation of IRS-1 was detectable during starvation, increased about twofold at 3 h after feeding and levels were maintained until 8 h. The content of the p85 subunit of PI 3-kinase associated with IRS-1 also increased after feeding in parallel with the changes in tyrosine phosphorylation of IRS-1. Tyrosine 286-294 insulin receptor substrate 1 Rattus norvegicus 219-224 9291837-6 1997 Because tyrosine phosphorylation of the insulin receptor beta-subunit and IRS-1 and the association of the p85 subunit of PI 3-kinase with IRS-1 in liver were closely correlated with the changes in the plasma concentration of insulin, we concluded that endogenous insulin secreted in response to eating caused these insulin-dependent intracellular changes in the liver. Tyrosine 8-16 insulin receptor substrate 1 Rattus norvegicus 40-79 9245706-4 1997 Insulin dramatically increased insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation (p < 0.05). Tyrosine 68-76 insulin receptor substrate 1 Rattus norvegicus 31-59 9245706-4 1997 Insulin dramatically increased insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation (p < 0.05). Tyrosine 68-76 insulin receptor substrate 1 Rattus norvegicus 61-66 9252480-4 1997 Tyrosine phosphorylation of the insulin receptor beta-subunit and the insulin receptor substrate 1 (IRS-1) was stimulated identically in cardiomyocytes from both lean and obese rats. Tyrosine 0-8 insulin receptor substrate 1 Rattus norvegicus 100-105 9496432-5 1997 After insulin stimulation the levels of insulin receptor and IRS-1 tyrosine phosphorylation were reduced to 79 +/- 5% (P < 0.005) and 58 +/- 6% (P < 0.0001), respectively, of the control (C) levels, in the remnant kidney. Tyrosine 67-75 insulin receptor substrate 1 Rattus norvegicus 61-66 9496432-9 1997 These data demonstrate that after unilateral nephrectomy there is a decrease in insulin-induced insulin receptor and IRS-1 tyrosine phosphorylation levels in kidney but not in liver and muscle. Tyrosine 123-131 insulin receptor substrate 1 Rattus norvegicus 117-122