PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 32337956-9 2020 Its overexpression also increased Grb2 expression and phosphorylation of AKT1 through elevation of IRS1 tyrosine phosphorylation in IRS1-transfected U-87 MG cells compared to control and mock transfected groups. Tyrosine 104-112 growth factor receptor bound protein 2 Homo sapiens 34-38 30923665-3 2019 Binding of Grb2 SH2 to the cytoplasmic region of CD28, phosphorylated Tyr (pY) containing the peptide motif pY-X-N-X, is required for costimulatory signaling in T cells. Tyrosine 70-73 growth factor receptor bound protein 2 Homo sapiens 11-15 31184863-3 2019 Upon FGFR activation, FRS2alpha undergoes phosphorylation on multiple tyrosines, triggering recruitment of the adaptor Grb2 and the tyrosine phosphatase Shp2, resulting in stimulation of PI3K/AKT and MAPK signaling pathways. Tyrosine 70-79 growth factor receptor bound protein 2 Homo sapiens 119-123 31844748-9 2019 Despite we don"t know the biological role coming from interaction between Grb2-SH2 domain and Coumarin, it is clear that this molecule could work in the same way as a SH2 domain inhibitor in order to block the link of Receptor Tyrosine kinases to Ras/MAPK pathway. Tyrosine 227-235 growth factor receptor bound protein 2 Homo sapiens 74-78 31759365-3 2019 Our aim is to explore regions outside the BCR-ABL oncoprotein to identify potential therapeutic targets to curb drug resistance by targeting growth factor receptor-bound protein-2 (Grb-2) which binds to BCR-ABL at the phosphorylated tyrosine (Y177) thereby activating the Ras and PI3K/AKT signaling pathway. Tyrosine 233-241 growth factor receptor bound protein 2 Homo sapiens 141-179 31759365-3 2019 Our aim is to explore regions outside the BCR-ABL oncoprotein to identify potential therapeutic targets to curb drug resistance by targeting growth factor receptor-bound protein-2 (Grb-2) which binds to BCR-ABL at the phosphorylated tyrosine (Y177) thereby activating the Ras and PI3K/AKT signaling pathway. Tyrosine 233-241 growth factor receptor bound protein 2 Homo sapiens 181-186 29453318-3 2018 Receptor tyrosine kinases (RTK), such as ErbB2, bind the ShcA PTB domain to promote breast tumorigenesis by engaging Grb2 downstream of the ShcA tyrosine phosphorylation sites to activate AKT/mTOR signaling. Tyrosine 9-17 growth factor receptor bound protein 2 Homo sapiens 117-121 28951535-2 2017 During signalosome assembly, members of the growth factor receptor-bound protein 2 (Grb2) family of cytosolic adaptor proteins bind cooperatively to LAT through interactions with its phosphorylated tyrosine (pTyr) residues. Tyrosine 198-206 growth factor receptor bound protein 2 Homo sapiens 44-82 29523808-4 2018 Using TALEN-mediated gene targeting, we show that in human B cells Grb2 and GRAP amplify signaling by the immunoglobulin tail tyrosine (ITT) motif of mIgE-containing BCRs and furthermore connect immunoreceptor tyrosine-based activation motif (ITAM) signaling to activation of the Ras-controlled Erk MAP kinase pathway. Tyrosine 126-134 growth factor receptor bound protein 2 Homo sapiens 67-71 29523808-4 2018 Using TALEN-mediated gene targeting, we show that in human B cells Grb2 and GRAP amplify signaling by the immunoglobulin tail tyrosine (ITT) motif of mIgE-containing BCRs and furthermore connect immunoreceptor tyrosine-based activation motif (ITAM) signaling to activation of the Ras-controlled Erk MAP kinase pathway. Tyrosine 210-218 growth factor receptor bound protein 2 Homo sapiens 67-71 29182244-5 2017 Results from a series of LAT constructs with combinatorial mutations of tyrosine residues reveal a previously unidentified allosteric mechanism in which the binding affinity of LAT:Grb2 depends on the phosphorylation at remote tyrosine sites. Tyrosine 72-80 growth factor receptor bound protein 2 Homo sapiens 181-185 29182244-5 2017 Results from a series of LAT constructs with combinatorial mutations of tyrosine residues reveal a previously unidentified allosteric mechanism in which the binding affinity of LAT:Grb2 depends on the phosphorylation at remote tyrosine sites. Tyrosine 227-235 growth factor receptor bound protein 2 Homo sapiens 181-185 28951535-2 2017 During signalosome assembly, members of the growth factor receptor-bound protein 2 (Grb2) family of cytosolic adaptor proteins bind cooperatively to LAT through interactions with its phosphorylated tyrosine (pTyr) residues. Tyrosine 198-206 growth factor receptor bound protein 2 Homo sapiens 84-88 27543756-0 2016 Role of Herpes simplex virus 1 VP11/12 tyrosine-based binding motifs for Src family kinases, p85, Grb2 and Shc in activation of the phosphoinositide 3-kinase-Akt pathway. Tyrosine 39-47 growth factor receptor bound protein 2 Homo sapiens 98-102 28690151-2 2017 The principal binding partner for tyrosine phosphorylation sites on ShcA is Grb2. Tyrosine 34-42 growth factor receptor bound protein 2 Homo sapiens 76-80 27927989-3 2017 Following phosphorylation of the tyrosine, the proteins growth factor receptor-bound protein 2 (Grb2), Grb2-related adaptor downstream of Shc (Gads), and p85 subunit of phosphoinositide 3-kinase may bind to pYMNM (where pY is phosphotyrosine) via their Src homology 2 (SH2) domains, leading to downstream signaling to distinct immune pathways. Tyrosine 33-41 growth factor receptor bound protein 2 Homo sapiens 56-94 27543756-2 2016 VP11/12 utilizes tyrosine-based motifs within its C-terminal region to bind the SH2 domains of Src family kinases, the p85 subunit of PI3 Kinase and Grb2, and the PTB domain of Shc. Tyrosine 17-25 growth factor receptor bound protein 2 Homo sapiens 149-153 26552706-10 2015 We propose that DNAM-1 promotes NK cell activation via an immunoreceptor tyrosine tail (ITT)-like motif coupling DNAM-1 to Grb2 and other downstream effectors. Tyrosine 73-81 growth factor receptor bound protein 2 Homo sapiens 123-127 26103942-5 2015 Phosphorylation of tyrosine 160 (Y160) on Grb2, or binding of a tyrosylphosphate-containing ligand to the SH2 domain of Grb2, results in dimer dissociation. Tyrosine 19-27 growth factor receptor bound protein 2 Homo sapiens 42-46 25413232-0 2014 The immunoglobulin tail tyrosine motif upgrades memory-type BCRs by incorporating a Grb2-Btk signalling module. Tyrosine 24-32 growth factor receptor bound protein 2 Homo sapiens 84-88 25961473-9 2015 Remarkably, tyrosine residues involved in Grb2 binding were heavily phosphorylated in a membrane-mimetic environment. Tyrosine 12-20 growth factor receptor bound protein 2 Homo sapiens 42-46 25535246-3 2015 This complex requires the adapter GRB2, which bridges SHP to THEMIS in a Tyr-phosphorylation-independent fashion. Tyrosine 73-76 growth factor receptor bound protein 2 Homo sapiens 34-38 25391654-3 2015 Phosphorylation of FAT on Tyr(925) facilitates FA disassembly and connects to the MAPK pathway through Grb2 association, but requires dissociation of the first helix (H1) of the four-helix bundle of FAT. Tyrosine 26-29 growth factor receptor bound protein 2 Homo sapiens 103-107 24265393-0 2014 Growth factor receptor-bound protein 2 contributes to (hem)immunoreceptor tyrosine-based activation motif-mediated signaling in platelets. Tyrosine 74-82 growth factor receptor bound protein 2 Homo sapiens 0-38 24248601-11 2014 These findings identify Grb2 as a new FAK activator and reveal its essential role in coordinating PTPalpha tyrosine phosphorylation to enable downstream integrin signaling and migration. Tyrosine 107-115 growth factor receptor bound protein 2 Homo sapiens 24-28 24265393-4 2014 OBJECTIVE: We tested the hypothesis that Grb2 is a crucial adapter protein in (hem)immunoreceptor tyrosine-based activation motif signaling in platelets. Tyrosine 98-106 growth factor receptor bound protein 2 Homo sapiens 41-45 24265393-8 2014 In vivo, this selective (hem)immunoreceptor tyrosine-based activation motif signaling defect resulted in prolonged bleeding times but affected arterial thrombus formation only after concomitant treatment with acetylsalicylic acid, indicating that defective glycoprotein VI signaling in the absence of Grb2 can be compensated through thromboxane A2-induced G protein-coupled receptor signaling pathways. Tyrosine 44-52 growth factor receptor bound protein 2 Homo sapiens 301-305 24265393-9 2014 CONCLUSIONS: These results reveal an important contribution of Grb2 in (hem)immunoreceptor tyrosine-based activation motif signaling in platelets in hemostasis and thrombosis by stabilizing the LAT signalosome. Tyrosine 91-99 growth factor receptor bound protein 2 Homo sapiens 63-67 24003223-6 2013 Three GAREM2 tyrosines (Tyr-102, Tyr-429, and Tyr-551) are phosphorylated upon EGF stimulation and are necessary for binding to Grb2. Tyrosine 13-22 growth factor receptor bound protein 2 Homo sapiens 128-132 24003223-6 2013 Three GAREM2 tyrosines (Tyr-102, Tyr-429, and Tyr-551) are phosphorylated upon EGF stimulation and are necessary for binding to Grb2. Tyrosine 24-27 growth factor receptor bound protein 2 Homo sapiens 128-132 24003223-6 2013 Three GAREM2 tyrosines (Tyr-102, Tyr-429, and Tyr-551) are phosphorylated upon EGF stimulation and are necessary for binding to Grb2. Tyrosine 33-36 growth factor receptor bound protein 2 Homo sapiens 128-132 24003223-6 2013 Three GAREM2 tyrosines (Tyr-102, Tyr-429, and Tyr-551) are phosphorylated upon EGF stimulation and are necessary for binding to Grb2. Tyrosine 33-36 growth factor receptor bound protein 2 Homo sapiens 128-132 24003223-9 2013 GAREM2 is expressed in some neuroblastoma cell lines and is also tyrosine-phosphorylated and bound to Grb2 after treatment with EGF. Tyrosine 65-73 growth factor receptor bound protein 2 Homo sapiens 102-106 23277357-5 2013 We demonstrate that Grb2 is required specifically downstream of Tyr(313), whereas the Tyr(239)/Tyr(240) phosphorylation sites require the Crk adaptor proteins to augment TGFbeta-induced migration and invasion. Tyrosine 64-67 growth factor receptor bound protein 2 Homo sapiens 20-24 23027125-5 2013 Specifically, HER2 overexpression blocks epidermal growth factor receptor (EGFR) tyrosine phosphorylation on Y1045 and Y1068, the known docking sites of c-Cbl and Grb2, respectively, whereas promoting phosphorylation on Y1173, the known docking site of the Gab adaptor proteins and phospholipase C gamma. Tyrosine 81-89 growth factor receptor bound protein 2 Homo sapiens 163-167 23826330-5 2013 Using a novel phosphopeptide microarray technology, we have mapped endogenous tyrosine-phosphoproteome interaction networks in breast cancer cells mediated by signaling adaptor protein GRB2, which transduces cellular responses downstream of several RTKs through the Ras-ERK signaling cascade. Tyrosine 78-86 growth factor receptor bound protein 2 Homo sapiens 185-189 23946459-0 2013 Role of herpes simplex virus VP11/12 tyrosine-based motifs in binding and activation of the Src family kinase Lck and recruitment of p85, Grb2, and Shc. Tyrosine 37-45 growth factor receptor bound protein 2 Homo sapiens 138-142 23946459-2 2013 The C-terminal region of VP11/12 contains tyrosine-based motifs predicted to bind the SH2 domains of SFKs (YETV and YEEI), p85 (YTHM), and Grb2 (YENV) and the phosphotyrosine-binding (PTB) domain of Shc (NPLY). Tyrosine 42-50 growth factor receptor bound protein 2 Homo sapiens 139-143 22828513-5 2012 Binding of Tyr phosphorylated AICD-47 ((P)AICD-47) to Grb2-SH2 domain was carried out by a favorable enthalpic change (DeltaH=-197.5+-6.2 kcal mole(-1) at 25 C) and an unfavorable entropic contribution (DeltaS=-631 cal mol(-1) deg(-1) at 25 C). Tyrosine 11-14 growth factor receptor bound protein 2 Homo sapiens 54-58 23150065-5 2012 The SH2 domain of Grb2 binds to growth factor receptors at phosphorylated tyrosine residues thus coupling receptor activation to the SOS-Ras-MAP kinase signaling cascade. Tyrosine 74-82 growth factor receptor bound protein 2 Homo sapiens 18-22 22683472-1 2012 Tyrosine autophosphorylation within the cytoplasmic tail of EGF-receptor is a key event, which in turn recruits several factors including Shc, Grb2 and Rin1 that are essential activities for receptor-mediated endocytosis and signaling. Tyrosine 0-8 growth factor receptor bound protein 2 Homo sapiens 143-147 22001015-4 2011 High-resolution crystal structures of Grb2-SH2 domain bound to AICD peptides reveal a unique mode of binding where the peptides assume a noncanonical conformation that is unlike other structures of AICD peptides bound to protein-tyrosine-binding domains or that of its free state; rather, a flipping of the C-terminal helix of AICD is evident. Tyrosine 229-237 growth factor receptor bound protein 2 Homo sapiens 38-42 22726438-6 2012 Upon stimulation, FGFR2 phosphorylates tyrosine residues on Grb2, promoting dissociation from the receptor and allowing full activation of downstream signaling. Tyrosine 39-47 growth factor receptor bound protein 2 Homo sapiens 60-64 22521882-8 2012 RESULTS: Tyrosine kinome profiling demonstrated upregulation of nine tyrosine kinases in tumors relative to matched normal thyroid tissue: EGFR, PTK6, BTK, HCK, ABL1, TNK1, GRB2, ERK, and SRC. Tyrosine 9-17 growth factor receptor bound protein 2 Homo sapiens 173-177 22027826-6 2011 Our biochemical study shows that EGF stimulation induces phosphorylation of tyrosine 733, which enables ACAP4 to bind Grb2. Tyrosine 76-84 growth factor receptor bound protein 2 Homo sapiens 118-122 21625213-6 2011 The shift from lysosomal degradation to recycling at the plasma membrane correlates with a reduced phosphorylation of the fibroblast growth factor receptor substrate-2alpha tyrosine 196, the major docking site for Grb2-Cbl complexes responsible for receptor ubiquitination and degradation. Tyrosine 173-181 growth factor receptor bound protein 2 Homo sapiens 214-218 22505611-6 2012 Here we show that the activation of plexin-B1 by Sema4D and its subsequent tyrosine phosphorylation by Met creates a docking site for the SH2 domain of growth factor receptor bound-2 (Grb2). Tyrosine 75-83 growth factor receptor bound protein 2 Homo sapiens 152-182 22505611-6 2012 Here we show that the activation of plexin-B1 by Sema4D and its subsequent tyrosine phosphorylation by Met creates a docking site for the SH2 domain of growth factor receptor bound-2 (Grb2). Tyrosine 75-83 growth factor receptor bound protein 2 Homo sapiens 184-188 22327338-5 2012 By analysis of the adaptor proteins NCK1 and GRB2 mutants we further show that the negative loop on p38 is mediated by c-ABL phosphorylation at tyrosine 105 of the adaptor protein NCK1, while the phosphorylation at tyrosine 209 of GRB2 down-modulates ERK1/2 and JNKs signaling. Tyrosine 144-152 growth factor receptor bound protein 2 Homo sapiens 45-49 22327338-5 2012 By analysis of the adaptor proteins NCK1 and GRB2 mutants we further show that the negative loop on p38 is mediated by c-ABL phosphorylation at tyrosine 105 of the adaptor protein NCK1, while the phosphorylation at tyrosine 209 of GRB2 down-modulates ERK1/2 and JNKs signaling. Tyrosine 144-152 growth factor receptor bound protein 2 Homo sapiens 231-235 22327338-5 2012 By analysis of the adaptor proteins NCK1 and GRB2 mutants we further show that the negative loop on p38 is mediated by c-ABL phosphorylation at tyrosine 105 of the adaptor protein NCK1, while the phosphorylation at tyrosine 209 of GRB2 down-modulates ERK1/2 and JNKs signaling. Tyrosine 215-223 growth factor receptor bound protein 2 Homo sapiens 45-49 22327338-5 2012 By analysis of the adaptor proteins NCK1 and GRB2 mutants we further show that the negative loop on p38 is mediated by c-ABL phosphorylation at tyrosine 105 of the adaptor protein NCK1, while the phosphorylation at tyrosine 209 of GRB2 down-modulates ERK1/2 and JNKs signaling. Tyrosine 215-223 growth factor receptor bound protein 2 Homo sapiens 231-235 20554525-5 2010 Here we show that active NPM-ALK, but not a kinase-dead mutant, bound and induced Grb2 phosphorylation in tyrosine 160. Tyrosine 106-114 growth factor receptor bound protein 2 Homo sapiens 82-86 21784853-2 2011 MET initiates intracellular signaling by autophosphorylation on specific cytoplasmic tyrosines that form docking sites for the adaptor proteins Grb2 and Gab1. Tyrosine 85-94 growth factor receptor bound protein 2 Homo sapiens 144-148 20933011-8 2011 Study of the FCRL6 association with signaling molecules showed its ability to recruit SHP-1, SHP-2, SHIP-1, and SHIP-2 phosphatases, and also adaptor protein Grb2 through phosphorylated cytoplasmic tyrosines. Tyrosine 198-207 growth factor receptor bound protein 2 Homo sapiens 158-162 20554525-6 2010 An intact SH3 domain at the C terminus of Grb2 was required for Tyr(160) phosphorylation. Tyrosine 64-67 growth factor receptor bound protein 2 Homo sapiens 42-46 20554525-7 2010 Furthermore, Grb2 did not bind to a single region but rather to different regions of NPM-ALK, mainly Tyr(152-156), Tyr(567), and a proline-rich region, Pro(415-417). Tyrosine 101-104 growth factor receptor bound protein 2 Homo sapiens 13-17 20554525-7 2010 Furthermore, Grb2 did not bind to a single region but rather to different regions of NPM-ALK, mainly Tyr(152-156), Tyr(567), and a proline-rich region, Pro(415-417). Tyrosine 115-118 growth factor receptor bound protein 2 Homo sapiens 13-17 19508206-3 2010 Recently, we discovered a peptide 1 (Fmoc-Glu-Tyr-Aib-Asn-NH(2)) with high affinity for the Grb2-SH2 domain by using surface plasmon resonance (SPR)-biosensor technology. Tyrosine 46-49 growth factor receptor bound protein 2 Homo sapiens 92-96 20644716-7 2010 Themis2 was inducibly tyrosine phosphorylated upon LPS challenge and interacted with Lyn kinase (P25911), the Rho guanine nucleotide exchange factor, Vav (P27870), and the adaptor protein Grb2 (Q60631). Tyrosine 22-30 growth factor receptor bound protein 2 Homo sapiens 188-192 20623096-6 2010 Recent research has also implicated Grb2 in tyrosine phosphorylation of PLD2 that also involves Sos and the ERK pathway. Tyrosine 44-52 growth factor receptor bound protein 2 Homo sapiens 36-40 19735729-2 2010 To date the SH2 domain of Grb2 has been shown to mediate receptor interactions with phosphorylated tyrosine residues sited directly on the receptor or on auxiliary docking proteins. Tyrosine 99-107 growth factor receptor bound protein 2 Homo sapiens 26-30 20398064-0 2010 Tyrosine phosphorylation of R3 subtype receptor-type protein tyrosine phosphatases and their complex formations with Grb2 or Fyn. Tyrosine 0-8 growth factor receptor bound protein 2 Homo sapiens 117-121 20398064-5 2010 Either Grb2 or Fyn, through their Src homology-2 domains, bound to the tyrosine-phosphorylated SAP-1. Tyrosine 71-79 growth factor receptor bound protein 2 Homo sapiens 7-11 20398064-7 2010 Tyrosine phosphorylation of VE-PTP or PTPRO also promoted their complex formations with Grb2 or Fyn. Tyrosine 0-8 growth factor receptor bound protein 2 Homo sapiens 88-92 20398064-10 2010 Our results thus suggest that tyrosine phosphorylation of R3 subtype RPTPs promotes their complex formations with Grb2 or Fyn and thus participates in the regulation of cell morphology. Tyrosine 30-38 growth factor receptor bound protein 2 Homo sapiens 114-118 17923684-4 2007 Upon engagement, Neph1 is phosphorylated on specific tyrosine residues by Fyn, which results in the recruitment of Grb2, an event that is necessary for Neph1-induced actin polymerization at the plasma membrane. Tyrosine 53-61 growth factor receptor bound protein 2 Homo sapiens 115-119 20006842-5 2009 As is the case for A36, YL126-mediated actin tail formation is enhanced by the recruitment of Grb2 via a single phosphorylated tyrosine in YL126. Tyrosine 127-135 growth factor receptor bound protein 2 Homo sapiens 94-98 19798056-2 2009 We show here that EGF stimulates transient tyrosine phosphorylation of Tom1L1 by the Src family kinases, resulting in transient interaction of Tom1L1 with the activated EGFR bridged by Grb2 and Shc. Tyrosine 43-51 growth factor receptor bound protein 2 Homo sapiens 185-189 19798056-8 2009 These results suggest that EGF triggers a transient Grb2/Shc-mediated association of EGFR with Tyr-phosphorylated Tom1L1 to engage the endocytic machinery for endocytosis of the ligand-receptor complex. Tyrosine 95-98 growth factor receptor bound protein 2 Homo sapiens 52-56 19682241-9 2009 The novel platelet adapter Dok-3 and the structurally related Dok-1 are tyrosine phosphorylated in an Src kinase-independent manner downstream of alphaIIbbeta3 in human platelets, leading to an interaction with Grb2 and SHIP-1. Tyrosine 72-80 growth factor receptor bound protein 2 Homo sapiens 211-215 19559020-5 2009 Furthermore, brefelamide diminished EGF-induced phosphorylation of EGF receptor at Tyr(1068), a Grb2 binding site that leads to an activation of the Ras/Raf/ERK system. Tyrosine 83-86 growth factor receptor bound protein 2 Homo sapiens 96-100 19509291-6 2009 In addition, the tyrosine phosphorylations of GAREM are necessary for its binding to Grb2. Tyrosine 17-25 growth factor receptor bound protein 2 Homo sapiens 85-89 19419970-4 2009 However, compared with other known glycan-binding receptors, the receptor contains an unusually large intracellular domain that consists of multiple sequence motifs, including phosphorylated tyrosine residues, that allow it to interact with signaling molecules such as Grb2. Tyrosine 191-199 growth factor receptor bound protein 2 Homo sapiens 269-273 19233262-3 2009 Here, we show that Gab2 is tyrosine phosphorylated in a Grb2-dependent manner downstream of activated VEGF receptor-2 (VEGFR2), and that it associates with signalling proteins including PI3K and SHP2, but apparently not with the receptor. Tyrosine 27-35 growth factor receptor bound protein 2 Homo sapiens 56-60 19273609-0 2009 Tyrosine phosphorylation of Grb2: role in prolactin/epidermal growth factor cross talk in mammary epithelial cell growth and differentiation. Tyrosine 0-8 growth factor receptor bound protein 2 Homo sapiens 28-32 19273609-5 2009 We identify tyrosine phosphorylation of the growth factor receptor-bound protein 2 (Grb2) as a critical mechanism by which PRL antagonizes EGF-induced cell proliferation by attenuating the activation of the Ras/mitogen-activated protein kinase (MAPK) pathway. Tyrosine 12-20 growth factor receptor bound protein 2 Homo sapiens 44-82 19273609-5 2009 We identify tyrosine phosphorylation of the growth factor receptor-bound protein 2 (Grb2) as a critical mechanism by which PRL antagonizes EGF-induced cell proliferation by attenuating the activation of the Ras/mitogen-activated protein kinase (MAPK) pathway. Tyrosine 12-20 growth factor receptor bound protein 2 Homo sapiens 84-88 19273609-6 2009 Together, our results define a novel negative cross-regulation between PRL and EGF involving the Jak2/Stat5a and Ras/MAPK pathways through tyrosine phosphorylation of Grb2. Tyrosine 139-147 growth factor receptor bound protein 2 Homo sapiens 167-171 18183397-1 2008 Autophosphorylation of tyrosine residues on the cytoplasmic tail of the epidermal growth factor receptor (EGFR) upon ligand binding leads to recruitment of the Grb2/Sos complex to the activated receptor and to activation of the Ras pathway. Tyrosine 23-31 growth factor receptor bound protein 2 Homo sapiens 160-164 17715395-9 2007 Epidermal growth factor receptor (EGFR) BRET structure-function studies identify the tyrosine residues 1068, 1114, and 1148 as the main residues mediating the interaction of EGFR with the adapter protein Grb2. Tyrosine 85-93 growth factor receptor bound protein 2 Homo sapiens 204-208 19668218-5 2009 When phosphorylated, this tyrosine recruited the adaptor Grb2, resulting in sustained protein kinase activation and prolonged generation of second messengers, which together culminated in enhanced B cell proliferation. Tyrosine 26-34 growth factor receptor bound protein 2 Homo sapiens 57-61 19427038-2 2009 TCR activation results in the tyrosine phosphorylation of LAT, leading to the direct interaction with several proteins, including PLC-gamma 1, Grb2 and Gads. Tyrosine 30-38 growth factor receptor bound protein 2 Homo sapiens 143-147 19289054-3 2009 Subsequent phosphorylation on Tyr-317 within the Shc linker region induces Shc interactions with Grb2-Son of Sevenless that initiate Ras-mitogen-activated protein kinase signaling. Tyrosine 30-33 growth factor receptor bound protein 2 Homo sapiens 97-101 18567737-5 2008 Furthermore, resveratrol inhibited PDGFR phosphorylation at the PI 3 kinase and Grb-2 binding sites tyrosine-751 and tyrosine-716, respectively. Tyrosine 100-108 growth factor receptor bound protein 2 Homo sapiens 80-85 18567737-5 2008 Furthermore, resveratrol inhibited PDGFR phosphorylation at the PI 3 kinase and Grb-2 binding sites tyrosine-751 and tyrosine-716, respectively. Tyrosine 117-125 growth factor receptor bound protein 2 Homo sapiens 80-85 17869481-3 2007 The SH2 domain of Grb2 binds the tyrosine phosphorylated lipovitellin1, a homologue of the human apolipoprotein B. Tyrosine 33-41 growth factor receptor bound protein 2 Homo sapiens 18-22 17986823-5 2007 Phosphorylation of multiple tyrosine residues results in the association of IRS-1 with the Src homology 2 (SH2) domains of other cytoplasmic signaling proteins, including phosphatidylinositol 3" kinase, Syp, Grb2 and Nck. Tyrosine 28-36 growth factor receptor bound protein 2 Homo sapiens 208-212 17689925-4 2007 We found that the binding between Sprouty2 and Grb2 is constitutive, independent of Sprouty2 tyrosine phosphorylation, although it is increased when fibroblast growth factor receptor is activated. Tyrosine 93-101 growth factor receptor bound protein 2 Homo sapiens 47-51 17991782-1 2007 Phosphorylation of the cytoplasmic tyrosine residues of the epidermal growth factor receptor (EGFR) upon binding of EGF induces recognition of various intracellular signaling molecules, including Grb2. Tyrosine 35-43 growth factor receptor bound protein 2 Homo sapiens 196-200 16702953-1 2006 The membrane-linked docking protein SNT-2/FRS2beta/FRS3 becomes tyrosine phosphorylated in response to fibroblast growth factors (FGFs) and neurotrophins and serves as a platform for recruitment of multiple signaling proteins, including Grb2 and Shp2, to FGF receptors or neurotrophin receptors. Tyrosine 64-72 growth factor receptor bound protein 2 Homo sapiens 237-241 17384289-2 2006 We have recently shown that tyrosine-phosphorylated APP and CTFs may interact with Grb2 and ShcA adaptor proteins and that this coupling occurs at a higher extent in AD subjects only. Tyrosine 28-36 growth factor receptor bound protein 2 Homo sapiens 83-87 16672218-2 2006 Upon stimulation via the antigen receptors, it is tyrosine-phosphorylated and binds Grb2 and the p85 subunit of phosphatidylinositol 3-kinase. Tyrosine 50-58 growth factor receptor bound protein 2 Homo sapiens 84-88 16787925-3 2006 We observed that the Grb2-bound adapter Gab1 is tyrosine-phosphorylated and relocated to membrane fractions upon VEGF stimulation of endothelial cells. Tyrosine 48-56 growth factor receptor bound protein 2 Homo sapiens 21-25 16941570-5 2006 Interestingly, the type I transmembrane protein G6f was found to be specifically phosphorylated on Tyr-281 in response to platelet activation by CRP, providing a docking site for the adapter Grb2. Tyrosine 99-102 growth factor receptor bound protein 2 Homo sapiens 191-195 16941570-7 2006 Further, we also demonstrate for the first time that Grb2 and its homolog Gads are tyrosine-phosphorylated in CRP-stimulated platelets. Tyrosine 83-91 growth factor receptor bound protein 2 Homo sapiens 53-57 16906159-4 2006 In T cells, the SH2 domain of GRB2 binds phosphorylated tyrosines on the adaptor protein LAT and the GRB2 SH3 domains associate with the proline-rich regions of SOS1 and CBL. Tyrosine 56-65 growth factor receptor bound protein 2 Homo sapiens 30-34 16725108-3 2006 BTLA has a third conserved tyrosine-containing motif within the cytoplasmic domain, similar in sequence to a Grb-2 recruitment site. Tyrosine 27-35 growth factor receptor bound protein 2 Homo sapiens 109-114 16509576-0 2006 Discovery of a novel nonphosphorylated pentapeptide motif displaying high affinity for Grb2-SH2 domain by the utilization of 3"-substituted tyrosine derivatives. Tyrosine 140-148 growth factor receptor bound protein 2 Homo sapiens 87-91 16581823-5 2006 SHP-1 and Grb2 interact with phosphorylated tyrosine residues within chB1r ITIM1 and ITIM2, respectively. Tyrosine 44-52 growth factor receptor bound protein 2 Homo sapiens 10-14 16241905-5 2006 NEU3 markedly enhanced tyrosine phosphorylation of integrin beta4 with recruitment of Shc and Grb-2 only on laminin-5, and NEU3 was co-immunoprecipitated by an anti-(integrin beta4) antibody, suggesting that association of NEU3 with integrin beta4 might facilitate promotion of the integrin-derived signalling on laminin-5. Tyrosine 23-31 growth factor receptor bound protein 2 Homo sapiens 94-99 16038803-0 2005 Grb2 negatively regulates epidermal growth factor-induced phospholipase C-gamma1 activity through the direct interaction with tyrosine-phosphorylated phospholipase C-gamma1. Tyrosine 126-134 growth factor receptor bound protein 2 Homo sapiens 0-4 16436051-5 2006 Here, we identified Grb2 as a Dok-3-binding protein upon its tyrosine phosphorylation. Tyrosine 61-69 growth factor receptor bound protein 2 Homo sapiens 20-24 16165154-1 2005 The high-affinity binding of the growth factor receptor-bound protein 2 (Grb2) SH2 domain to tyrosine-phosphorylated cytosolic domains of receptor tyrosine kinases (RTKs) is an attractive target for therapeutic intervention in many types of cancer. Tyrosine 93-101 growth factor receptor bound protein 2 Homo sapiens 33-71 16165154-1 2005 The high-affinity binding of the growth factor receptor-bound protein 2 (Grb2) SH2 domain to tyrosine-phosphorylated cytosolic domains of receptor tyrosine kinases (RTKs) is an attractive target for therapeutic intervention in many types of cancer. Tyrosine 93-101 growth factor receptor bound protein 2 Homo sapiens 73-77 16038803-3 2005 In this study, we demonstrate for the first time that Grb2, an adaptor protein, specifically interacts with tyrosine-phosphorylated PLC-gamma1 at Tyr783. Tyrosine 108-116 growth factor receptor bound protein 2 Homo sapiens 54-58 16038803-5 2005 Replacement of Tyr783 with Phe completely blocked EGF-induced interaction of PLC-gamma1 with Grb2, indicating that tyrosine phosphorylation of PLC-gamma1 at Tyr783 is essential for the interaction with Grb2. Tyrosine 115-123 growth factor receptor bound protein 2 Homo sapiens 93-97 16038803-5 2005 Replacement of Tyr783 with Phe completely blocked EGF-induced interaction of PLC-gamma1 with Grb2, indicating that tyrosine phosphorylation of PLC-gamma1 at Tyr783 is essential for the interaction with Grb2. Tyrosine 115-123 growth factor receptor bound protein 2 Homo sapiens 202-206 16038803-6 2005 Interestingly, the depletion of Grb2 from HEK-293 cells by RNA interference significantly enhanced increased EGF-induced PLC-gamma1 enzymatic activity and mobilization of the intracellular Ca2+, while it did not affect EGF-induced tyrosine phosphorylation of PLC-gamma1. Tyrosine 231-239 growth factor receptor bound protein 2 Homo sapiens 32-36 15687335-7 2005 Insulin-induced tyrosine phosphorylation of SNP5-SHIP2 was decreased compared with that of wild-type SHIP2, resulting in increased Shc/Grb2 association and MAPK activation. Tyrosine 16-24 growth factor receptor bound protein 2 Homo sapiens 135-139 15879090-6 2005 We mapped this interaction showing that the Src homology 2 domain of Grb2 and the tyrosine residue Y606 in CD229 are required for CD229-Grb2 complex formation. Tyrosine 82-90 growth factor receptor bound protein 2 Homo sapiens 136-140 15677445-6 2005 A constitutive complex of Grb2 and Cbl could be recruited to both receptor isoforms via docking of Shc to phosphorylated Tyr-1062 in RET. Tyrosine 121-124 growth factor receptor bound protein 2 Homo sapiens 26-30 15677445-8 2005 In addition, phosphorylation of Tyr-1096, which is present in RET51 but absent in RET9, endowed the longer isoform with a second route to recruit the Grb2.Cbl complex. Tyrosine 32-35 growth factor receptor bound protein 2 Homo sapiens 150-154 15688026-3 2005 Tyrosine residues 239/240 and 317 become phosphorylated following receptor engagement and, as such, form two Grb2 binding sites, which have been proposed to be differentially coupled to Myc-dependent survival and to fos-dependent proliferation, respectively. Tyrosine 0-8 growth factor receptor bound protein 2 Homo sapiens 109-113 15813734-6 2005 These tyrosines differentially contribute to actin polymerization in a fashion reminiscent of actin "tail" formation mediated by the vaccinia virus envelope protein A36R, which utilizes two similarly spaced phosphotyrosines to recruit the adaptors Nck and Grb2, respectively, in order to stimulate N-WASP. Tyrosine 6-15 growth factor receptor bound protein 2 Homo sapiens 256-260 15611048-6 2005 In addition, Tom1L1 possesses several tyrosine motifs at the C-terminal region that mediate interactions with members of the Src family kinases and other signaling proteins such as Grb2 and p85. Tyrosine 38-46 growth factor receptor bound protein 2 Homo sapiens 181-185 15486046-12 2005 In summary, 1) SHIP-WT and SHIPDeltaIP expression inhibit insulin and PDGF stimulated Ras, MAPK kinase, and MAPK activities; 2) SHIP associates with tyrosine phosphorylated Shc, and the proline-rich sequences in SHIP associate with Grb2 and titrate out SOS to form Shc*Grb2*SHIP complexes; and 3) dissociation of SOS from the Shc*Grb2 complex inhibits Ras GTP loading, leading to decreased signaling through the MAPK pathway. Tyrosine 149-157 growth factor receptor bound protein 2 Homo sapiens 269-273 15709155-7 2005 Phosphorylation of Thr-Glu-Tyr, but not Tyr, was decreased by inhibitors of protein tyrosine kinase and Grb2-SH2. Tyrosine 27-30 growth factor receptor bound protein 2 Homo sapiens 104-108 15389579-6 2005 High affinity FGF2 receptors were up-regulated in Apert osteoblasts and analysis of signal transduction showed elevated levels of Grb2 tyrosine phosphorylation and the Grb2-p85 beta association, which FGF2 stimulation strongly reduced. Tyrosine 135-143 growth factor receptor bound protein 2 Homo sapiens 130-134 15471854-8 2004 The tyrosine-phosphorylated Y(60)TNP was previously identified as an SH2 site for Grb2 binding, and we found that mutation of Tyr(60) blocked coimmunoprecipitation of the chimera with Grb2. Tyrosine 4-12 growth factor receptor bound protein 2 Homo sapiens 82-86 15536091-6 2005 Enzyme-linked immunosorbent assays confirmed the interaction between the SH2 domain of Grb2 and a tyrosine-phosphorylated MAP-2 peptide spanning the pY(67)SN motif. Tyrosine 98-106 growth factor receptor bound protein 2 Homo sapiens 87-91 15486046-12 2005 In summary, 1) SHIP-WT and SHIPDeltaIP expression inhibit insulin and PDGF stimulated Ras, MAPK kinase, and MAPK activities; 2) SHIP associates with tyrosine phosphorylated Shc, and the proline-rich sequences in SHIP associate with Grb2 and titrate out SOS to form Shc*Grb2*SHIP complexes; and 3) dissociation of SOS from the Shc*Grb2 complex inhibits Ras GTP loading, leading to decreased signaling through the MAPK pathway. Tyrosine 149-157 growth factor receptor bound protein 2 Homo sapiens 232-236 15486046-12 2005 In summary, 1) SHIP-WT and SHIPDeltaIP expression inhibit insulin and PDGF stimulated Ras, MAPK kinase, and MAPK activities; 2) SHIP associates with tyrosine phosphorylated Shc, and the proline-rich sequences in SHIP associate with Grb2 and titrate out SOS to form Shc*Grb2*SHIP complexes; and 3) dissociation of SOS from the Shc*Grb2 complex inhibits Ras GTP loading, leading to decreased signaling through the MAPK pathway. Tyrosine 149-157 growth factor receptor bound protein 2 Homo sapiens 269-273 15471854-8 2004 The tyrosine-phosphorylated Y(60)TNP was previously identified as an SH2 site for Grb2 binding, and we found that mutation of Tyr(60) blocked coimmunoprecipitation of the chimera with Grb2. Tyrosine 4-12 growth factor receptor bound protein 2 Homo sapiens 184-188 15471854-8 2004 The tyrosine-phosphorylated Y(60)TNP was previously identified as an SH2 site for Grb2 binding, and we found that mutation of Tyr(60) blocked coimmunoprecipitation of the chimera with Grb2. Tyrosine 126-129 growth factor receptor bound protein 2 Homo sapiens 82-86 15471854-8 2004 The tyrosine-phosphorylated Y(60)TNP was previously identified as an SH2 site for Grb2 binding, and we found that mutation of Tyr(60) blocked coimmunoprecipitation of the chimera with Grb2. Tyrosine 126-129 growth factor receptor bound protein 2 Homo sapiens 184-188 15659814-5 2004 BACE1 expression is upregulated in AD brain, and we have recently shown in human brain and in vitro that BACE product CTFs, when phosphorylated in tyrosine residues, interact with the adaptor proteins ShcA and Grb2, which usually are involved in signal transduction pathways. Tyrosine 147-155 growth factor receptor bound protein 2 Homo sapiens 210-214 15456754-0 2004 Two distinct tyrosine-based motifs enable the inhibitory receptor FcgammaRIIB to cooperatively recruit the inositol phosphatases SHIP1/2 and the adapters Grb2/Grap. Tyrosine 13-21 growth factor receptor bound protein 2 Homo sapiens 154-158 15659815-2 2004 Tyrosine phosphorylation generates a substrate that is sequentially bound by the adaptor proteins ShcA and Grb2, and this interaction is significantly enhanced in Alzheimer"s disease brains. Tyrosine 0-8 growth factor receptor bound protein 2 Homo sapiens 107-111 15659815-6 2004 In summary, our data suggest that in SH-SY5Y cells, tyrosine-phosphorylated APP is involved in a complex with ShcA-Grb2 adaptors that is disrupted during apoptosis. Tyrosine 52-60 growth factor receptor bound protein 2 Homo sapiens 115-119 15351743-2 2004 We previously reported that tyrosine 1062 in RET receptor tyrosine kinase activated by glial cell line-derived neurotrophic factor (GDNF) represents a binding site for the Shc-Grb2-Gab1 complex, and that the p85 subunit of phosphatidylinositol 3-kinase (PI3K) and SHP2 tyrosine phosphatase is associated with Gab1 in GDNF-treated cells. Tyrosine 28-36 growth factor receptor bound protein 2 Homo sapiens 176-180 15130480-1 2004 The focal adhesion targeting (FAT) domain of focal adhesion kinase (FAK) is critical for recruitment of FAK to focal adhesions and contains tyrosine 926, which, when phosphorylated, binds the SH2 domain of Grb2. Tyrosine 140-148 growth factor receptor bound protein 2 Homo sapiens 206-210 15272025-6 2004 The activated SHP-2 then dephosphorylated IRS-1 Tyr(P)-895, resulting in blockade of the pathways from IRS-1/Grb2/Sos to the ERK and p38 MAPK. Tyrosine 48-51 growth factor receptor bound protein 2 Homo sapiens 109-113 15341520-3 2004 Among others, the interaction between tyrosine-phosphorylated CTFs and ShcA-Grb2 adaptors is highly enhanced in AD brain. Tyrosine 38-46 growth factor receptor bound protein 2 Homo sapiens 76-80 15054097-0 2004 Growth factor receptor-bound protein 2 interaction with the tyrosine-phosphorylated tail of amyloid beta precursor protein is mediated by its Src homology 2 domain. Tyrosine 60-68 growth factor receptor bound protein 2 Homo sapiens 0-38 15054097-6 2004 Here we describe a protein, growth factor receptor-bound protein 2 (Grb2), that specifically binds AbetaPP, phosphorylated in Tyr(682). Tyrosine 126-129 growth factor receptor bound protein 2 Homo sapiens 28-66 15054097-6 2004 Here we describe a protein, growth factor receptor-bound protein 2 (Grb2), that specifically binds AbetaPP, phosphorylated in Tyr(682). Tyrosine 126-129 growth factor receptor bound protein 2 Homo sapiens 68-72 15151996-6 2004 Tyrosine phosphorylation of Dok was associated with increased binding to Grb2. Tyrosine 0-8 growth factor receptor bound protein 2 Homo sapiens 73-77 15143164-2 2004 Here, we demonstrate direct binding of Grb2 to the Tel-Abl (ETV6-Abl) fusion protein, the product of complex (9;12) chromosomal translocations in human leukemia, via tyrosine 314 encoded by TEL exon 5. Tyrosine 166-174 growth factor receptor bound protein 2 Homo sapiens 39-43 14722116-4 2004 In this study, we utilized various LAB Tyr to Phe mutants to map the phosphorylation and Grb2-binding sites of LAB. Tyrosine 39-42 growth factor receptor bound protein 2 Homo sapiens 89-93 15029250-2 2004 Phosphorylation of LAT at multiple tyrosines creates binding sites for the adaptors Gads and Grb2, leading to nucleation of multiprotein signaling complexes. Tyrosine 35-44 growth factor receptor bound protein 2 Homo sapiens 93-97 15029250-7 2004 The structures reveal the basis for preferential recognition of specific LAT sites by Gads, as well as for the relatively greater promiscuity of the related adaptor Grb2, whose binding also requires asparagine at position +2 C-terminal to the phosphorylated tyrosine. Tyrosine 258-266 growth factor receptor bound protein 2 Homo sapiens 165-169 14722116-7 2004 Mutation of these three tyrosines abolished Grb2 binding and LAB function. Tyrosine 24-33 growth factor receptor bound protein 2 Homo sapiens 44-48 14498832-4 2003 Since Ras-MAPK and STAT pathways are simultaneously stimulated by EGF, and Tyr-1086 and Tyr-1068 of EGFR are reported to be the binding sites for both Grb2 and Stat3, we investigated the possible regulatory role of Grb2 in STAT activation. Tyrosine 75-78 growth factor receptor bound protein 2 Homo sapiens 151-155 14679214-6 2004 A tyrosine-phosphorylated peptide of the epidermal growth factor receptor specifically retrieved the Src homology domain (SH) 2- and SH3 domain-containing adapter protein Grb2. Tyrosine 2-10 growth factor receptor bound protein 2 Homo sapiens 171-175 14652006-10 2003 Thus, similar to the bisphosphoryl tyrosine-based activation motif (BTAM) by which the Grb-2 associated binder (Gab1), PDGF receptor, and PECAM-1 recruit SHP-2, BTLA also relies on dual ITIMs for its association with the phosphatases SHP-1 and SHP-2. Tyrosine 35-43 growth factor receptor bound protein 2 Homo sapiens 87-92 14498832-4 2003 Since Ras-MAPK and STAT pathways are simultaneously stimulated by EGF, and Tyr-1086 and Tyr-1068 of EGFR are reported to be the binding sites for both Grb2 and Stat3, we investigated the possible regulatory role of Grb2 in STAT activation. Tyrosine 88-91 growth factor receptor bound protein 2 Homo sapiens 151-155 14498832-5 2003 In the present study, we report that transient expression of Grb2 specifically down-regulates EGF-stimulated tyrosine phosphorylation of Stat3, which leads to a repression of Stat3 transcriptional activity. Tyrosine 109-117 growth factor receptor bound protein 2 Homo sapiens 61-65 14498832-6 2003 In contrast, depletion of Grb2 by RNA interference substantially increases Stat3 tyrosine phosphorylation induced by EGF. Tyrosine 81-89 growth factor receptor bound protein 2 Homo sapiens 26-30 12766170-7 2003 Alternatively, the structural integrity of the Met receptor, and residues upstream of Tyr-1349 located in the C-terminal lobe of the kinase domain, are required for Grb2-independent interaction with the Gab1 MBD. Tyrosine 86-89 growth factor receptor bound protein 2 Homo sapiens 165-169 12852788-3 2003 This tyrosine residue is found in a consensus-binding motif (YXN) for the Src homology 2 domains of Grb2 and Grb7 (where Grb stands for growth-factor-receptor-bound protein). Tyrosine 5-13 growth factor receptor bound protein 2 Homo sapiens 100-104 12149261-9 2002 In addition, we report a slight action of LMW-PTP on Tyr-716, which directs MAPK activation through Grb2 binding. Tyrosine 53-56 growth factor receptor bound protein 2 Homo sapiens 100-104 12878216-4 2003 To understand the structural basis for the high-affinity binding of these novel non-phosphorus-containing inhibitors to the Grb2-SH2 domain, we extensively studied herein the unique functional requirements of the acidic side chain in Tyr-2 position due to the absence of the phosphate group in these non-phosphorylated peptides. Tyrosine 234-237 growth factor receptor bound protein 2 Homo sapiens 124-128 12837289-5 2003 Here we demonstrate that treatment of vascular smooth muscle cells with angiotensin II results in activation of the Shc/Grb2/ERK2 signaling pathway as measured by (1) increased Shc tyrosine phosphorylation, (2) increased c-Src/Shc cellular co-localization, (3) increased Shc/Grb2 co-association, and (4) ERK2 activation. Tyrosine 181-189 growth factor receptor bound protein 2 Homo sapiens 120-124 12496416-5 2003 Grb2, Gads, and PLC-gamma1 associated with LAT preferentially via different sets of tyrosine residues; however, they failed to interact with LAT mutants containing only one tyrosine. Tyrosine 84-92 growth factor receptor bound protein 2 Homo sapiens 0-4 12220227-1 2002 Signalling by the insulin receptor substrate (IRS) proteins is critically dependent on the tyrosine phosphorylation of specific binding sites that recruit Src homology 2 (SH2)-domain-containing proteins, such as the p85 subunit of phosphoinositide 3-kinase (PI 3-kinase), the tyrosine phosphatase SHP-2 and the adapter protein Grb2. Tyrosine 91-99 growth factor receptor bound protein 2 Homo sapiens 327-331 12485888-0 2002 Signal transduction through tyrosine-phosphorylated carboxy-terminal fragments of APP via an enhanced interaction with Shc/Grb2 adaptor proteins in reactive astrocytes of Alzheimer"s disease brain. Tyrosine 28-36 growth factor receptor bound protein 2 Homo sapiens 123-127 12485888-6 2002 Grb2 also is involved in complexes with ShcA and tyrosine-phosphorylated CTFs, and in AD brain the interaction between Grb2-ShcA and CTFs is enhanced. Tyrosine 49-57 growth factor receptor bound protein 2 Homo sapiens 0-4 12171928-7 2002 Mutational analysis revealed that tyrosine 271 in SKAP55 played a pivotal role for interaction with both Fyn kinase and adapter protein Grb-2, indicating that the Fyn-phosphorylated SKAP55 transiently associates with adapter Grb-2 to mediate mitogen-activated protein kinase activation. Tyrosine 34-42 growth factor receptor bound protein 2 Homo sapiens 136-141 12171928-7 2002 Mutational analysis revealed that tyrosine 271 in SKAP55 played a pivotal role for interaction with both Fyn kinase and adapter protein Grb-2, indicating that the Fyn-phosphorylated SKAP55 transiently associates with adapter Grb-2 to mediate mitogen-activated protein kinase activation. Tyrosine 34-42 growth factor receptor bound protein 2 Homo sapiens 225-230 12748850-11 2003 The tyrosine-phosphorylated EGFR was immunoprecipitated together with GRB2 and tyrosine-phosphorylated Shc, indicating that transactivated EGFR is able to generate downstream signals. Tyrosine 4-12 growth factor receptor bound protein 2 Homo sapiens 70-74 12444928-4 2003 We have recently demonstrated that Tyr-936 is an autophosphorylation site involved in binding the adapter proteins Grb2 and Grb7. Tyrosine 35-38 growth factor receptor bound protein 2 Homo sapiens 115-119 12531430-3 2003 Using transient co-overexpression studies of the prolactin receptor (PRLR) and several tyrosine to phenylalanine mutants of SHP-2, we show that grb2 associates with SHP-2 through the C-terminal tyrosine residues of SHP-2, Y(546) and Y(584). Tyrosine 87-95 growth factor receptor bound protein 2 Homo sapiens 144-148 12531430-3 2003 Using transient co-overexpression studies of the prolactin receptor (PRLR) and several tyrosine to phenylalanine mutants of SHP-2, we show that grb2 associates with SHP-2 through the C-terminal tyrosine residues of SHP-2, Y(546) and Y(584). Tyrosine 194-202 growth factor receptor bound protein 2 Homo sapiens 144-148 12631709-3 2003 Interestingly, mutations of tyrosine phosphorylation sites 1068 and 1086 that interact with growth-factor-receptor-binding protein Grb2 completely abolished receptor internalization in PAE cells. Tyrosine 28-36 growth factor receptor bound protein 2 Homo sapiens 131-135 12359715-5 2002 However, like LAT, LAX has tyrosine motifs for binding Grb2, Gads, and the p85 subunit of phosphatidylinositol 3-kinase. Tyrosine 27-35 growth factor receptor bound protein 2 Homo sapiens 55-59 12007418-4 2002 Recruitment of Nck and Grb2 to viral particles requires phosphorylation of tyrosine residues 112 and 132 of A36R, the vaccinia actin tail nucleator, respectively. Tyrosine 75-83 growth factor receptor bound protein 2 Homo sapiens 23-27 12084708-0 2002 Signal transduction through tyrosine-phosphorylated C-terminal fragments of amyloid precursor protein via an enhanced interaction with Shc/Grb2 adaptor proteins in reactive astrocytes of Alzheimer"s disease brain. Tyrosine 28-36 growth factor receptor bound protein 2 Homo sapiens 139-143 11923305-8 2002 This involves serine phosphorylation-dependent differential modulation of the affinity of Tyr(P)789 for the Src and Grb2 SH2 domains. Tyrosine 90-93 growth factor receptor bound protein 2 Homo sapiens 116-120 12162872-4 2002 To assess the role of some FGF signaling molecules involved in FGFR2 regulation, we studied Grb2 tyrosine phosphorylation and the phosphotyrosine proteins associated with Grb2. Tyrosine 97-105 growth factor receptor bound protein 2 Homo sapiens 92-96 11997436-3 2002 Here, we demonstrate that Grb2 bound to tyrosine-phosphorylated FRS2 alpha forms a ternary complex with Cbl by means of its Src homology 3 domains resulting in the ubiquitination of fibroblast growth factor (FGF) receptor and FRS2 alpha in response to FGF stimulation. Tyrosine 40-48 growth factor receptor bound protein 2 Homo sapiens 26-30 11874466-3 2002 Recruitment of GRB2 by tyrosine-phosphorylated proteins in response to TPO and convulxin but not by thrombin occurred with a similar time-course to RAS activation, consistent with a causal relationship. Tyrosine 23-31 growth factor receptor bound protein 2 Homo sapiens 15-19 12112020-8 2002 Sam68 is constitutively associated with the SH3 domains of Grb2 and it does not change upon insulin stimulation, but Sam68 is Tyr-phosphorylated and promotes the association of GAP with the Grb2-SOS complex. Tyrosine 126-129 growth factor receptor bound protein 2 Homo sapiens 59-63 11882361-1 2002 OBJECTIVE: Following activation of T cells, phosphorylation of tyrosine residues occurs through a complex signaling process involving protein tyrosine kinases, phosphatases, and a variety of adapter molecules including Grb2. Tyrosine 63-71 growth factor receptor bound protein 2 Homo sapiens 219-223 11741929-6 2002 This was confirmed in vitro for Hck, Lck, and Grb2, which showed enhanced association with tyrosine-phosphorylated glutathione S-transferase-ADAM15 cytoplasmic domain compared with unphosphorylated protein. Tyrosine 91-99 growth factor receptor bound protein 2 Homo sapiens 46-50 11818515-3 2002 Grb2, Ras(p21), Raf and MEK inhibitors dose-dependently prevented sperm capacitation and protein tyrosine phosphorylation, without modifying sperm O(2)(-)* production. Tyrosine 97-105 growth factor receptor bound protein 2 Homo sapiens 0-4 12112020-8 2002 Sam68 is constitutively associated with the SH3 domains of Grb2 and it does not change upon insulin stimulation, but Sam68 is Tyr-phosphorylated and promotes the association of GAP with the Grb2-SOS complex. Tyrosine 126-129 growth factor receptor bound protein 2 Homo sapiens 190-194 11457888-3 2001 In the Jurkat T cell line, the distal four tyrosines of LAT bind PLCgamma-1, Grb2, and Gads. Tyrosine 43-52 growth factor receptor bound protein 2 Homo sapiens 77-81 11713219-3 2001 IGF-1-induced tyrosine phosphorylation of Shc and its subsequent association with Grb2 were increased in WT-Shc cells, whereas they were decreased in 3F-Shc cells compared with those in parental L6 cells. Tyrosine 14-22 growth factor receptor bound protein 2 Homo sapiens 82-86 11786178-6 2001 3/The patterns of the association of the adaptor protein, Grb2 with tyrosine phosphorylated proteins following cell stimulation with the bi-phosphorylated membrane proximal or the central ITAMs were similar, while the membrane distal ITAM was unable to induce any of these associations. Tyrosine 68-76 growth factor receptor bound protein 2 Homo sapiens 58-62 11551923-6 2001 The tyrosine residue in CD22 required for Grb2 recruitment (Tyr-828) is distinct and independent from the two ITIM tyrosines required for efficient SHP-1 recruitment (Tyr-843 and Tyr-863). Tyrosine 4-12 growth factor receptor bound protein 2 Homo sapiens 42-46 11551923-6 2001 The tyrosine residue in CD22 required for Grb2 recruitment (Tyr-828) is distinct and independent from the two ITIM tyrosines required for efficient SHP-1 recruitment (Tyr-843 and Tyr-863). Tyrosine 60-63 growth factor receptor bound protein 2 Homo sapiens 42-46 11500516-3 2001 The transforming potential of at least two of these autophosphorylation sites (Tyr(1144) and Tyr(1226/1227)) has been further correlated with their ability to associate with Grb2 and Shc adapter proteins, respectively. Tyrosine 79-82 growth factor receptor bound protein 2 Homo sapiens 174-178 11500516-3 2001 The transforming potential of at least two of these autophosphorylation sites (Tyr(1144) and Tyr(1226/1227)) has been further correlated with their ability to associate with Grb2 and Shc adapter proteins, respectively. Tyrosine 93-96 growth factor receptor bound protein 2 Homo sapiens 174-178 11792427-6 2002 CD2 crosslinking markedly induced tyrosine phosphorylation of Cbl associated with Grb2 or CrkL, Shc and LAT, compared with IL-2 stimulation. Tyrosine 34-42 growth factor receptor bound protein 2 Homo sapiens 82-86 11792427-8 2002 In vitro binding studies using GST-fusion proteins revealed that interactions of Grb2-Shc and CrkL-Cbl were mediated through each SH2 domain in tyrosine phosphorylation-dependent manner. Tyrosine 144-152 growth factor receptor bound protein 2 Homo sapiens 81-85 11726515-0 2001 Tyrosine phosphorylation of Grb2 by Bcr/Abl and epidermal growth factor receptor: a novel regulatory mechanism for tyrosine kinase signaling. Tyrosine 0-8 growth factor receptor bound protein 2 Homo sapiens 28-32 11726515-2 2001 We found that Grb2 was tyrosine-phosphorylated in cells expressing BCR/ABL and in A431 cells stimulated with epidermal growth factor (EGF). Tyrosine 23-31 growth factor receptor bound protein 2 Homo sapiens 14-18 11726515-4 2001 Tyr209 within the C-terminal SH3 domain of Grb2 was identified as one of the tyrosine phosphorylation sites, and phosphorylation of Tyr209 abolished the binding of the SH3 domain to a proline-rich Sos peptide in vitro. Tyrosine 77-85 growth factor receptor bound protein 2 Homo sapiens 43-47 11726515-6 2001 These results suggest that tyrosine phosphorylation of Grb2 is a novel mechanism of down-regulation of tyrosine kinase signaling. Tyrosine 27-35 growth factor receptor bound protein 2 Homo sapiens 55-59 11753673-6 2001 Tyrosine phosphorylation stimulates PI3K and PLCgamma-1 enzymatic activity, and on ShcA creates binding sites for Grb2 with its associated Sos1 and Gab1. Tyrosine 0-8 growth factor receptor bound protein 2 Homo sapiens 114-118 11394873-3 2001 We found that (i) upon PDGF stimulation, Lad expression is induced in lung cells, especially in the bronchial epithelial cells; (ii) Lad is tyrosine phosphorylated upon PDGF stimulation and is associated with PDGF receptor; (iii) upon PDGF stimulation, Grb2 is recruited to Lad in human embryonic lung cells; (iv) overexpression of Lad elevated AP-1 promoter activity by two- to threefold, whereas dominant negative Lad abrogated PDGF-dependent activation of AP-1 promoter. Tyrosine 140-148 growth factor receptor bound protein 2 Homo sapiens 253-257 11416032-6 2001 We found that ATA and EB mimicked the IGF-I effect on tyrosine phosphorylation of the IGF-I receptor (IGF-IR) and its major substrates, insulin receptor substrate-1 (IRS-1) and IRS-2; induced the association of these substrates with phosphatidylinositol 3-kinase and Grb2; and activated Akt kinase and p42/p44 mitogen-activated protein kinases. Tyrosine 54-62 growth factor receptor bound protein 2 Homo sapiens 267-271 11278488-4 2001 Co-expression studies in human 293T cells showed that v-Src could associate with and phosphorylate a Phe-397 FAK mutant at Tyr-925 promoting Grb2 binding to FAK in suspended cells. Tyrosine 123-126 growth factor receptor bound protein 2 Homo sapiens 141-145 11402314-1 2001 In this study, we show that upon thrombopoietin (Tpo) stimulation the two adapter proteins Gab1 and Gab2 are strongly tyrosine phosphorylated and associated with Shc, SHP2, PI 3-kinase and Grb2 in mpl-expressing UT7 cells. Tyrosine 118-126 growth factor receptor bound protein 2 Homo sapiens 189-193 11278639-3 2001 Upon HGF binding, several tyrosines within the intracellular domain of its receptor, c-Met, become phosphorylated and mediate the binding of effector proteins, such as Grb2. Tyrosine 26-35 growth factor receptor bound protein 2 Homo sapiens 168-172 11353842-3 2001 We demonstrate that tyrosine phosphorylation of FRS2alpha leads to Grb2-mediated complex formation with the docking protein Gab1 and its tyrosine phosphorylation, resulting in the recruitment and activation of PI3-kinase. Tyrosine 20-28 growth factor receptor bound protein 2 Homo sapiens 67-71 11353842-3 2001 We demonstrate that tyrosine phosphorylation of FRS2alpha leads to Grb2-mediated complex formation with the docking protein Gab1 and its tyrosine phosphorylation, resulting in the recruitment and activation of PI3-kinase. Tyrosine 137-145 growth factor receptor bound protein 2 Homo sapiens 67-71 11353842-4 2001 Furthermore, Grb2 bound to tyrosine-phosphorylated FRS2 through its SH2 domain interacts primarily via its carboxyl-terminal SH3 domain with a proline-rich region in Gab1 and via its amino-terminal SH3 domain with the nucleotide exchange factor Sos1. Tyrosine 27-35 growth factor receptor bound protein 2 Homo sapiens 13-17 11278982-6 2001 Consistent with this observation, H(2)O(2) stimulated EGFR tyrosine phosphorylation and complex formation with Shc-Grb2 that was abolished by PP2, implicating Src in H(2)O(2)-induced EGFR activation. Tyrosine 59-67 growth factor receptor bound protein 2 Homo sapiens 115-119 11369229-9 2001 Analysis of E89K/Delta Grb2 mutant fibroblasts revealed a marked defect in ERK/MAP kinase activation and Gab1 tyrosine phosphorylation following growth factor stimulation. Tyrosine 110-118 growth factor receptor bound protein 2 Homo sapiens 23-27 10938266-5 2000 By using a neutralizing antibody or dominant negative (DN) strategies or specific inhibitors, we also show that activation of Janus kinase Jak2 by autocrine secretion of PRL is one of the significant components of constitutive tyrosine phosphorylation of ErbB-2, its association with Grb2 and activation of mitogen-activated protein (MAP) kinase in human breast cancer cell lines that overexpress ErbB-2. Tyrosine 227-235 growth factor receptor bound protein 2 Homo sapiens 284-288 11399323-7 2000 Immunodepletion studies reveal that Grb2-associated tyrosine phosphorylated p120 kDa protein is Cbl. Tyrosine 52-60 growth factor receptor bound protein 2 Homo sapiens 36-40 11263968-0 2001 L-selectin tyrosine phosphorylates cbl and induces association of tyrosine-phosphorylated cbl with crkl and grb2. Tyrosine 11-19 growth factor receptor bound protein 2 Homo sapiens 108-112 11263968-0 2001 L-selectin tyrosine phosphorylates cbl and induces association of tyrosine-phosphorylated cbl with crkl and grb2. Tyrosine 66-74 growth factor receptor bound protein 2 Homo sapiens 108-112 11263968-6 2001 There is an activation induced association of tyrosine phosphorylated Cbl with Grb2 and CrkL, respectively, but not CrkII. Tyrosine 46-54 growth factor receptor bound protein 2 Homo sapiens 79-83 10995764-9 2000 These results indicate that upon ligand stimulation, at least two distinct protein complexes assemble on phosphorylated Tyr-1062 of c-Ret via Shc, one leading to activation of the Ras/Erk pathway through recruitment of Grb2/Sos and another to the PI3K/Akt pathway through recruitment of Grb2/Gab2 followed by p85(PI3K) and SHP-2. Tyrosine 120-123 growth factor receptor bound protein 2 Homo sapiens 219-223 10995764-9 2000 These results indicate that upon ligand stimulation, at least two distinct protein complexes assemble on phosphorylated Tyr-1062 of c-Ret via Shc, one leading to activation of the Ras/Erk pathway through recruitment of Grb2/Sos and another to the PI3K/Akt pathway through recruitment of Grb2/Gab2 followed by p85(PI3K) and SHP-2. Tyrosine 120-123 growth factor receptor bound protein 2 Homo sapiens 287-291 11169415-4 2000 Moreover, tyrosine phosphorylation of LAT led to the recruitment of intracytoplasmic signaling molecules including phospholipase Cgamma and Grb2. Tyrosine 10-18 growth factor receptor bound protein 2 Homo sapiens 140-144 10938266-7 2000 Our results indicate that autocrine secretion of PRL stimulates tyrosine phosphorylation of ErbB-2 by Jak2, provides docking sites for Grb2 and stimulates Ras-MAP kinase cascade, thereby causing unrestricted cellular proliferation. Tyrosine 64-72 growth factor receptor bound protein 2 Homo sapiens 135-139 11027663-4 2000 They interact with tyrosine-phosphorylated Shp-2, p85, Grb2, and Shc. Tyrosine 19-27 growth factor receptor bound protein 2 Homo sapiens 55-59 10908310-4 2000 First, we report that PDGF stimulates the G(i)-mediated tyrosine phosphorylation of the Grb-2 adaptor protein, Gab1. Tyrosine 56-64 growth factor receptor bound protein 2 Homo sapiens 88-93 11002419-4 2000 In response to GDNF stimulation, SHC bound to GAB1 and GRB2 adaptor proteins as well as RET, and SHC and GAB1 were highly phosphorylated on tyrosine. Tyrosine 140-148 growth factor receptor bound protein 2 Homo sapiens 55-59 11002419-5 2000 The complex formation consisting of SHC, GAB1 and GRB2 was almost abolished by replacement of tyrosine 1062 in RET with phenylalanine. Tyrosine 94-102 growth factor receptor bound protein 2 Homo sapiens 50-54 11075717-7 2000 Both tyrosine-phosphorylated Shc and IRS can bind to Grb2, but Shc . Tyrosine 5-13 growth factor receptor bound protein 2 Homo sapiens 53-57 10749687-14 2000 Furthermore, Pyk2, as well as FAK, might have one or more important roles in post-aggregation tyrosine phosphorylation events, in association with the cytoskeleton and through interaction with adapter proteins including Grb2 and Shc. Tyrosine 94-102 growth factor receptor bound protein 2 Homo sapiens 220-224 10749687-0 2000 Involvement of proline-rich tyrosine kinase 2 in platelet activation: tyrosine phosphorylation mostly dependent on alphaIIbbeta3 integrin and protein kinase C, translocation to the cytoskeleton and association with Shc through Grb2. Tyrosine 28-36 growth factor receptor bound protein 2 Homo sapiens 227-231 10681590-4 2000 The subsequent tyrosine phosphorylation of LAT (linker for activation of T cell) by ZAP-70 leads to a shift in equilibrium from the ZAP-70.Grb-2.SOS(Vav) complex to the (Vav)SOS.Grb-2.LAT complex. Tyrosine 15-23 growth factor receptor bound protein 2 Homo sapiens 139-144 10753897-6 2000 Interestingly, priming of chemoattractant-induced ERK activation is accompanied by an increase in association of tyrosine-phosphorylated proteins with the adapter protein Grb2. Tyrosine 113-121 growth factor receptor bound protein 2 Homo sapiens 171-175 10681590-4 2000 The subsequent tyrosine phosphorylation of LAT (linker for activation of T cell) by ZAP-70 leads to a shift in equilibrium from the ZAP-70.Grb-2.SOS(Vav) complex to the (Vav)SOS.Grb-2.LAT complex. Tyrosine 15-23 growth factor receptor bound protein 2 Homo sapiens 178-183 10660611-3 2000 Erythropoietin (EPO), the primary regulator of erythropoiesis, has been shown to activate the tyrosine phosphorylation of Shc, resulting in recruitment of Grb2. Tyrosine 94-102 growth factor receptor bound protein 2 Homo sapiens 155-159 10660611-5 2000 EPO activates the tyrosine phosphorylation of Ship1, resulting in the interdependent recruitment of Shc and Grb2. Tyrosine 18-26 growth factor receptor bound protein 2 Homo sapiens 108-112 10660596-8 2000 Further studies revealed that the adaptor protein GRB2 strongly promoted the formation of a stable protein complex between tyrosine-phosphorylated IRS-1 and catalytically inactive PTP1B, increasing their co-immunoprecipitation from an equimolar solution by 13.5 +/- 3.3-fold (n = 7; p < 0.01). Tyrosine 123-131 growth factor receptor bound protein 2 Homo sapiens 50-54 10544028-0 1999 Structural requirements for Tyr in the consensus sequence Y-E-N of a novel nonphosphorylated inhibitor to the Grb2-SH2 domain. Tyrosine 28-31 growth factor receptor bound protein 2 Homo sapiens 110-114 10660596-9 2000 Inclusion of GRB2 in a reaction mixture of IRS-1 and active PTP1B also increased the overall rate of IRS-1 tyrosine dephosphorylation by 2.7-3.9-fold (p < 0.01). Tyrosine 107-115 growth factor receptor bound protein 2 Homo sapiens 13-17 10567214-6 1999 The truncated fragments were tyrosine-phosphorylated under resting conditions, and associated with the signalling intermediates Shc and Grb2. Tyrosine 29-37 growth factor receptor bound protein 2 Homo sapiens 136-140 10570290-5 1999 Tyrosine-phosphorylated Shc, mainly the p52 isoform, was observed to transiently onload to the membrane Grb2-Sos complex on FcgammaRI stimulation. Tyrosine 0-8 growth factor receptor bound protein 2 Homo sapiens 104-108 10570290-6 1999 Cross-linking of FcgammaRI induces the tyrosine phosphorylation of Cbl, which forms a complex with Grb2 and Shc via the Cbl C terminus. Tyrosine 39-47 growth factor receptor bound protein 2 Homo sapiens 99-103 10570290-8 1999 The Src family tyrosine kinase inhibitor, PP1, was shown to completely inhibit Shc tyrosine phosphorylation, the Shc-Grb2 interaction, and the FcgammaR-induced respiratory burst. Tyrosine 15-23 growth factor receptor bound protein 2 Homo sapiens 117-121 10597315-4 1999 When stably expressed in K562 cells, SHIP was found to be constitutively tyrosine phosphorylated and associated with endogenous Shc and Grb-2. Tyrosine 73-81 growth factor receptor bound protein 2 Homo sapiens 136-141 10544028-4 1999 In this study we judiciously altered and incorporated various natural and unnatural amino acids as Tyr replacements within the -YEN- motif, and we demonstrate the functional importance and structural requirement of Tyr(3) for effective binding of this novel non-phosphorylated ligand to the Grb2-SH2 domain. Tyrosine 215-218 growth factor receptor bound protein 2 Homo sapiens 291-295 10438919-2 1999 Coordinate activation of these pathways is dependent on Lck- and ZAP-70-mediated tyrosine phosphorylation of a 36-kDa linker for activation of T cells and subsequent recruitment of phospholipase C-gamma1, Grb2-SOS, and SLP-76-vav. Tyrosine 81-89 growth factor receptor bound protein 2 Homo sapiens 205-209 10521483-6 1999 Mutation of this site abrogates binding of Grb2 and Grb7 to Tek in vivo, and this site is required for tyrosine phosphorylation of Grb7 and p85 in vivo. Tyrosine 103-111 growth factor receptor bound protein 2 Homo sapiens 43-47 10319320-5 1999 The VEGF-induced tyrosine phosphorylation of the VEGF receptor, Flk-1, and its association with the Shc/Grb2/Ras-GAP (guanosine triphosphatase-activating protein) complex were unaffected by 16K hPRL treatment. Tyrosine 17-25 growth factor receptor bound protein 2 Homo sapiens 104-108 10377264-0 1999 Identification of Tyr-703 and Tyr-936 as the primary association sites for Grb2 and Grb7 in the c-Kit/stem cell factor receptor. Tyrosine 30-33 growth factor receptor bound protein 2 Homo sapiens 75-79 10377264-2 1999 We furthermore demonstrate that the adapter protein Grb2 is a specific binding partner for both phosphorylated Tyr-703 and phosphorylated Tyr-936, whereas the adapter protein Grb7 binds selectively to phosphorylated Tyr-936. Tyrosine 111-114 growth factor receptor bound protein 2 Homo sapiens 52-56 10377264-2 1999 We furthermore demonstrate that the adapter protein Grb2 is a specific binding partner for both phosphorylated Tyr-703 and phosphorylated Tyr-936, whereas the adapter protein Grb7 binds selectively to phosphorylated Tyr-936. Tyrosine 138-141 growth factor receptor bound protein 2 Homo sapiens 52-56 10377264-2 1999 We furthermore demonstrate that the adapter protein Grb2 is a specific binding partner for both phosphorylated Tyr-703 and phosphorylated Tyr-936, whereas the adapter protein Grb7 binds selectively to phosphorylated Tyr-936. Tyrosine 138-141 growth factor receptor bound protein 2 Homo sapiens 52-56 10377264-4 1999 Binding of Grb2 to Tyr-703 in the c-Kit/SCFR provides a link to the Ras/mitogen-activated protein kinase pathway. Tyrosine 19-22 growth factor receptor bound protein 2 Homo sapiens 11-15 10377264-0 1999 Identification of Tyr-703 and Tyr-936 as the primary association sites for Grb2 and Grb7 in the c-Kit/stem cell factor receptor. Tyrosine 18-21 growth factor receptor bound protein 2 Homo sapiens 75-79 10405761-2 1999 Previous work in our laboratory established that Bcr is a major transformation-related substrate for the v-Fps tyrosine kinase, and tyrosine phosphorylation of Bcr induces Bcr-Grb-2/SOS association in vivo through the Src homology 2 (SH2) domain of Grb-2. Tyrosine 111-119 growth factor receptor bound protein 2 Homo sapiens 176-181 10405761-2 1999 Previous work in our laboratory established that Bcr is a major transformation-related substrate for the v-Fps tyrosine kinase, and tyrosine phosphorylation of Bcr induces Bcr-Grb-2/SOS association in vivo through the Src homology 2 (SH2) domain of Grb-2. Tyrosine 111-119 growth factor receptor bound protein 2 Homo sapiens 249-254 10405761-4 1999 Tyrosine phosphorylation of Bcr by Fes greatly enhanced the binding of Bcr to the SH2 domains of multiple signalling molecules in vitro, including Grb-2, Ras GTPase activating protein, phospholipase C-gamma, the 85,000 M(r) subunit of phosphatidylinositol 3"-kinase, and the Abl tyrosine kinase. Tyrosine 0-8 growth factor receptor bound protein 2 Homo sapiens 147-152 10400318-8 1999 Interestingly, when the phage display peptides were then phosphorylated on tyrosine, their affinity for GRB2 increased dramatically. Tyrosine 75-83 growth factor receptor bound protein 2 Homo sapiens 104-108 10021361-1 1999 BACKGROUND: The adaptor protein Gads is a Grb2-related protein originally identified on the basis of its interaction with the tyrosine-phosphorylated form of the docking protein Shc. Tyrosine 126-134 growth factor receptor bound protein 2 Homo sapiens 42-46 10209041-7 1999 Moreover, tyrosine-phosphorylated LAT/pp36/38 in detergent lysates prepared from anti-CD3 stimulated T cells associated with Grb2 but not GrpL. Tyrosine 10-18 growth factor receptor bound protein 2 Homo sapiens 125-129 10204582-7 1999 SLP-76, a recently cloned Grb2-associated protein, was strongly tyrosine phosphorylated after Fc gammaRI stimulation and was associated with both Cbl and Grb2. Tyrosine 64-72 growth factor receptor bound protein 2 Homo sapiens 26-30 9872323-2 1998 Phosphorylation of Shc tyrosine residues 239 and 317 leads to recruitment of the Grb2-Sos complex, thus linking Shc phosphorylation to Ras activation. Tyrosine 23-31 growth factor receptor bound protein 2 Homo sapiens 81-85 9764818-5 1998 In this study, by performing classical inhibition experiments using synthetic phosphopeptides and by site-directed mutagenesis of the putative docking site, we have determined that for Grb2 the latter is provided by the tyrosine 620 of Ret/ptc2 long isoform (corresponding to Tyr 1096 on proto-Ret). Tyrosine 220-228 growth factor receptor bound protein 2 Homo sapiens 185-189 9748249-5 1998 Furthermore, we showed that a mutation in the Grb2 binding site Tyr-925 of FAK partially abolishes its increase in HGF-induced phosphorylation. Tyrosine 64-67 growth factor receptor bound protein 2 Homo sapiens 46-50 9832424-8 1998 Treatment with PI 3-K inhibitors induced an increased association of IRS-2 with Grb2, probably as a result of the increased IRS-2 tyrosine phosphorylation. Tyrosine 130-138 growth factor receptor bound protein 2 Homo sapiens 80-84 9804835-4 1998 Moreover, tyrosine phosphorylation of Gab1 correlated with the binding of several SH2-containing signaling proteins to Gab1 including Shc, Grb2, phosphatidylinositol 3-kinase, and the SHP-2 tyrosine phosphatase. Tyrosine 10-18 growth factor receptor bound protein 2 Homo sapiens 139-143 9731041-8 1998 The binding was reduced when lysates from collagen-stimulated platelets were incubated with GST-Grb2, suggesting that tyrosine phosphorylation of WASP may directly or indirectly modulate the adapter function of WASP. Tyrosine 118-126 growth factor receptor bound protein 2 Homo sapiens 96-100 9764818-5 1998 In this study, by performing classical inhibition experiments using synthetic phosphopeptides and by site-directed mutagenesis of the putative docking site, we have determined that for Grb2 the latter is provided by the tyrosine 620 of Ret/ptc2 long isoform (corresponding to Tyr 1096 on proto-Ret). Tyrosine 276-279 growth factor receptor bound protein 2 Homo sapiens 185-189 9716598-2 1998 SLP-76, Cbl, Shc, and Grb2 have been implicated in immunoreceptor tyrosine-based activation motif (ITAM) signaling, leading to activation of Ras. Tyrosine 66-74 growth factor receptor bound protein 2 Homo sapiens 22-26 9607818-8 1998 Since dynamin constitutively associates with Grb2, it could be recruited to the insulin signaling complex through binding of Grb2 to tyrosine-phosphorylated Shc. Tyrosine 133-141 growth factor receptor bound protein 2 Homo sapiens 45-49 9636164-6 1998 Furthermore, Ang II caused rapid tyrosine phosphorylation of Shc and its association with Grb2. Tyrosine 33-41 growth factor receptor bound protein 2 Homo sapiens 90-94 9694876-8 1998 We propose a model whereby the association of Grb2 with CD28 occurs via an inducible SH3-mediated interaction and leads to the recruitment of tyrosine-phosphorylated proteins such as p52(shc) bound to the SH2 domain of Grb2. Tyrosine 142-150 growth factor receptor bound protein 2 Homo sapiens 46-50 9694876-8 1998 We propose a model whereby the association of Grb2 with CD28 occurs via an inducible SH3-mediated interaction and leads to the recruitment of tyrosine-phosphorylated proteins such as p52(shc) bound to the SH2 domain of Grb2. Tyrosine 142-150 growth factor receptor bound protein 2 Homo sapiens 219-223 9607818-8 1998 Since dynamin constitutively associates with Grb2, it could be recruited to the insulin signaling complex through binding of Grb2 to tyrosine-phosphorylated Shc. Tyrosine 133-141 growth factor receptor bound protein 2 Homo sapiens 125-129 9790226-5 1998 Moreover, by also using dominant negative JAK2 and in vitro kinase assay, we demonstrated that tyrosine 1068 of EGFR was evidently one of the major phosphorylation and Grb2 binding sites stimulated by GH via JAK2. Tyrosine 95-103 growth factor receptor bound protein 2 Homo sapiens 168-172 9590251-0 1998 CBL-GRB2 interaction in myeloid immunoreceptor tyrosine activation motif signaling. Tyrosine 47-55 growth factor receptor bound protein 2 Homo sapiens 4-8 9590251-4 1998 Fc gammaRI cross-linking of U937IF cells induces the tyrosine phosphorylation of CBL that is associated with an altered CBL-GRB2 interaction. Tyrosine 53-61 growth factor receptor bound protein 2 Homo sapiens 124-128 9673410-3 1998 The phosphorylated tyrosine at 1009 is a binding site for Syp/PTP1D, an adaptor molecule mediating Grb2/RAS signalling. Tyrosine 19-27 growth factor receptor bound protein 2 Homo sapiens 99-103 9566877-0 1998 Multiple Grb2-mediated integrin-stimulated signaling pathways to ERK2/mitogen-activated protein kinase: summation of both c-Src- and focal adhesion kinase-initiated tyrosine phosphorylation events. Tyrosine 165-173 growth factor receptor bound protein 2 Homo sapiens 9-13 9566877-3 1998 FN stimulation of NIH 3T3 fibroblasts promotes c-Src and FAK association in the Triton-insoluble cell fraction, and the time course of FN-stimulated ERK2 activation paralleled that of Grb2 binding to FAK at Tyr-925 and Grb2 binding to Shc. Tyrosine 207-210 growth factor receptor bound protein 2 Homo sapiens 184-188 9529333-4 1998 When expressed in 293T human fibroblast cells and tyrosine-phosphorylated, pp36 associated with phospholipase Cgamma-1 and Grb2. Tyrosine 50-58 growth factor receptor bound protein 2 Homo sapiens 123-127 9560226-4 1998 Furthermore, we identify two tyrosine residues that are subject to phosphorylation in response to muscarinic signaling and show that this phosphorylation induces two cytosolic proteins, c-Src and Grb2, to bind to PYK2. Tyrosine 29-37 growth factor receptor bound protein 2 Homo sapiens 196-200 9417079-8 1998 Further, tyrosine phosphorylation of Vav and the costimulation-dependent activation of Jun N-terminal kinase was blocked in cells defective in CD28/Grb2 binding. Tyrosine 9-17 growth factor receptor bound protein 2 Homo sapiens 148-152 9480847-6 1998 Thus, in cells transformed by v-Src, tyrosine phosphorylation of FGFR-1 results not in the expected association with PLC gamma and p90, but rather in the recruitment of the Ras activating Shc/Grb2/Sos complex. Tyrosine 37-45 growth factor receptor bound protein 2 Homo sapiens 192-196 9541596-4 1998 Our results indicate that stimulation of NK cells through CD16 results in a rapid tyrosine phosphorylation of Cbl, which is constitutively associated with Grb2 and forms an activation-dependent complex with the p85 subunit of Pl-3K. Tyrosine 82-90 growth factor receptor bound protein 2 Homo sapiens 155-159 9541596-5 1998 In addition, we detected the presence of the Grb2-associated tyrosine-phosphorylated p36 and Shc proteins in anti-Cbl and anti-p85 immunoprecipitates from CD16-stimulated NK cell lysates. Tyrosine 61-69 growth factor receptor bound protein 2 Homo sapiens 45-49 9489702-2 1998 Here we report the cloning of the cDNA for a highly tyrosine-phosphorylated 36-38 kDa protein, previously characterized by its association with Grb2, phospholipase C-gamma1, and the p85 subunit of phosphoinositide 3-kinase. Tyrosine 52-60 growth factor receptor bound protein 2 Homo sapiens 144-148 9374537-5 1997 We found that such a shear stress increased the tyrosine phosphorylation and the kinase activity of focal adhesion kinase (FAK) and its association with growth factor receptor binding protein 2 (Grb2) in a rapid and transient manner, suggesting that FAK may be linked to these mitogen-activated protein kinase signaling pathways through a Grb2. Tyrosine 48-56 growth factor receptor bound protein 2 Homo sapiens 153-193 9769703-6 1998 These phosphorylated tyrosines form binding sites for various signaling molecules that are themselves thought to be phosphorylated by JAK kinases, including 1) signal transducers and activators of transcription (Stats), which regulate transcription; 2) She proteins that recruit Grb2-SOS complexes, thereby initiating the Ras-MAP kinase pathway; and 3) insulin receptor substrate (IRS) proteins that are thought to regulate metabolic events in the cell. Tyrosine 21-30 growth factor receptor bound protein 2 Homo sapiens 279-283 9419966-4 1997 Stimulation of PDGFR"s and EGFR"s induced tyrosine phosphorylation of the Shc adaptor protein and its association with Grb2, suggesting a mechanism by which Ras may be activated in human malignant astrocytoma cells. Tyrosine 42-50 growth factor receptor bound protein 2 Homo sapiens 119-123 9434624-6 1997 SHC was tyrosine phosphorylated in response to Fc gamma RI stimulation of U937IF cells and bound to the SH2 domain of GRB2 in a stimulation-dependent manner. Tyrosine 8-16 growth factor receptor bound protein 2 Homo sapiens 118-122 9374537-5 1997 We found that such a shear stress increased the tyrosine phosphorylation and the kinase activity of focal adhesion kinase (FAK) and its association with growth factor receptor binding protein 2 (Grb2) in a rapid and transient manner, suggesting that FAK may be linked to these mitogen-activated protein kinase signaling pathways through a Grb2. Tyrosine 48-56 growth factor receptor bound protein 2 Homo sapiens 195-199 9374537-5 1997 We found that such a shear stress increased the tyrosine phosphorylation and the kinase activity of focal adhesion kinase (FAK) and its association with growth factor receptor binding protein 2 (Grb2) in a rapid and transient manner, suggesting that FAK may be linked to these mitogen-activated protein kinase signaling pathways through a Grb2. Tyrosine 48-56 growth factor receptor bound protein 2 Homo sapiens 339-343 9355745-4 1997 After binding to EGFR, PTP1B becomes tyrosine-phosphorylated at Tyr-66, a site that conforms to the consensus binding sequence for the Src homology 2 (SH2) domains of the adapter protein Grb2. Tyrosine 37-45 growth factor receptor bound protein 2 Homo sapiens 187-191 9378963-2 1997 We have previously demonstrated that CD16 ligation promotes complex formation between tyrosine-phosphorylated shc and Grb2, leading to activation of ras signaling pathway in human NK cells. Tyrosine 86-94 growth factor receptor bound protein 2 Homo sapiens 118-122 9378963-6 1997 Our data show that, while engagement of both receptors induces tyrosine phosphorylation of shc and Grb2 recruitment, shc-SH2/receptor complex association is evident only in CD16-zeta but not in CD16-gamma transfectants. Tyrosine 63-71 growth factor receptor bound protein 2 Homo sapiens 99-103 9368064-0 1997 Growth factors stimulate tyrosine dephosphorylation of p75 and its dissociation from the SH2 domain of Grb2. Tyrosine 25-33 growth factor receptor bound protein 2 Homo sapiens 103-107 9368064-2 1997 The binding of proteins to the SH2 domain of Grb2 has been reported to occur mainly after they are tyrosine-phosphorylated following receptor activation. Tyrosine 99-107 growth factor receptor bound protein 2 Homo sapiens 45-49 9363897-5 1997 Moreover, tyrosine at residue 1,068 of the EGFR is proposed to be one of the principal phosphorylation sites and Grb2-binding sites stimulated by growth hormone via Jak2. Tyrosine 10-18 growth factor receptor bound protein 2 Homo sapiens 113-117 9345034-5 1997 Further characterization of these tyrosine phosphorylated molecules revealed that Shc, Grb2, and SOS form a complex with the activated FLT4 receptor. Tyrosine 34-42 growth factor receptor bound protein 2 Homo sapiens 87-91 9326613-7 1997 The tyrosine phosphorylation of caldesmon, and its association with the Shc-Grb2-Sos signaling complex directly links tyrosine kinase oncogenic signaling events with cytoskeletal regulatory processes, and may define one mechanism regulating actin stress fiber disassembly in transformed cells. Tyrosine 4-12 growth factor receptor bound protein 2 Homo sapiens 76-80 9355745-4 1997 After binding to EGFR, PTP1B becomes tyrosine-phosphorylated at Tyr-66, a site that conforms to the consensus binding sequence for the Src homology 2 (SH2) domains of the adapter protein Grb2. Tyrosine 64-67 growth factor receptor bound protein 2 Homo sapiens 187-191 9254654-6 1997 The tyrosine phosphorylated SHPTP2 was complexed with the adapter protein Grb2 in IL-5-stimulated eosinophils. Tyrosine 4-12 growth factor receptor bound protein 2 Homo sapiens 74-78 9281317-3 1997 Inhibition of PLC-gamma1 tyrosine phosphorylation by phenylarsine oxide reduces the co-immunoprecipitation of PLC-gamma1 with GRB2. Tyrosine 25-33 growth factor receptor bound protein 2 Homo sapiens 126-130 9281317-4 1997 Furthermore, angiotensin II, a G protein-coupled receptor agonist, also induces the tyrosine phosphorylation of PLC-gamma1 and its co-immunoprecipitation with GRB2 in WB cells. Tyrosine 84-92 growth factor receptor bound protein 2 Homo sapiens 159-163 9281317-7 1997 In vitro studies further demonstrate that the Tyr771 and Tyr783 region of PLC-gamma1 and the SH2 domain of GRB2 are potentially involved in the tyrosine phosphorylation-dependent association between PLC-gamma1 and GRB2. Tyrosine 144-152 growth factor receptor bound protein 2 Homo sapiens 107-111 9281317-7 1997 In vitro studies further demonstrate that the Tyr771 and Tyr783 region of PLC-gamma1 and the SH2 domain of GRB2 are potentially involved in the tyrosine phosphorylation-dependent association between PLC-gamma1 and GRB2. Tyrosine 144-152 growth factor receptor bound protein 2 Homo sapiens 214-218 9242692-3 1997 We have previously demonstrated that a single carboxyl-terminal tyrosine residue, Tyr489, is essential for efficient transformation of Fr3T3 fibroblasts by Tpr-Met and forms a multisubstrate binding site for Grb2, phosphatidylinositol 3" kinase, phospholipase Cgamma, SHP2, and an unknown protein of 110 kDa. Tyrosine 64-72 growth factor receptor bound protein 2 Homo sapiens 208-212 9242692-6 1997 Moreover, we show that tyrosine phosphorylation of the Cbl protooncogene product as well as Gab1 required Tyr489 and correlated with the ability of Tpr-Met to associate with Grb2 and to transform cells, providing evidence that pathways downstream of Gab1 and/or Cbl may play a role in Tpr-Met-mediated cell transformation. Tyrosine 23-31 growth factor receptor bound protein 2 Homo sapiens 174-178 9205064-10 1997 In summary, this work provides the first evidence that in MCF-7 cells, cytostatic effects of Tam are associated with the modulation of IGF-IR signaling, specifically with: (a) down-regulation of IGF-I-induced tyrosine phosphorylation of the IGF-IR; (b) inhibition of IRS-1/phosphatidylinositol 3"-kinase signaling; and (c) up-regulation of SHC tyrosine phosphorylation and increased SHC/GRB2 binding. Tyrosine 209-217 growth factor receptor bound protein 2 Homo sapiens 387-391 9230117-2 1997 We have recently reported that gastrin stimulates the tyrosine phosphorylation of Shc proteins and their subsequent association with the Grb2/Sos complex, leading to mitogen-activated protein kinase (MAPK) activation, a pathway known to play an important role in cell proliferation. Tyrosine 54-62 growth factor receptor bound protein 2 Homo sapiens 137-141 9230117-5 1997 Our results indicate that Shc proteins are tyrosine phosphorylated and associate with Grb2 in response to phorbol esters, suggesting that activation of PKC is a potential signalling pathway leading to activation of the Shc/Grb2 complex. Tyrosine 43-51 growth factor receptor bound protein 2 Homo sapiens 86-90 9230117-5 1997 Our results indicate that Shc proteins are tyrosine phosphorylated and associate with Grb2 in response to phorbol esters, suggesting that activation of PKC is a potential signalling pathway leading to activation of the Shc/Grb2 complex. Tyrosine 43-51 growth factor receptor bound protein 2 Homo sapiens 223-227 9233773-3 1997 APS is structurally similar to SH2-B, an SH2 protein that potentially binds to the immunoreceptor tyrosine-based activation motif (ITAM) as well as Lnk which is postulated to be a signal transducer that links T-cell receptor to phospholipase Cgamma, Grb2 and phosphatidylinositol 3-kinase. Tyrosine 98-106 growth factor receptor bound protein 2 Homo sapiens 250-254 9205064-10 1997 In summary, this work provides the first evidence that in MCF-7 cells, cytostatic effects of Tam are associated with the modulation of IGF-IR signaling, specifically with: (a) down-regulation of IGF-I-induced tyrosine phosphorylation of the IGF-IR; (b) inhibition of IRS-1/phosphatidylinositol 3"-kinase signaling; and (c) up-regulation of SHC tyrosine phosphorylation and increased SHC/GRB2 binding. Tyrosine 344-352 growth factor receptor bound protein 2 Homo sapiens 387-391 9148935-2 1997 Focal adhesion kinase (FAK) associates with integrin receptors, and FN-stimulated phosphorylation of FAK at Tyr-397 and Tyr-925 promotes the binding of Src family PTKs and Grb2, respectively. Tyrosine 108-111 growth factor receptor bound protein 2 Homo sapiens 172-176 9185541-0 1997 Tyrosine phosphorylation of nicotinic acetylcholine receptor mediates Grb2 binding. Tyrosine 0-8 growth factor receptor bound protein 2 Homo sapiens 70-74 9185541-9 1997 These data suggest a novel role for tyrosine phosphorylation of the AChR in the initiation of a Grb2-mediated signaling cascade at the postsynaptic membrane. Tyrosine 36-44 growth factor receptor bound protein 2 Homo sapiens 96-100 9178760-6 1997 Competitive inhibition of substrate binding and mutagenesis experiments with EGFR/Ufo constructs revealed C-terminal tyrosine 821 (EILpYVNMDEG) as a docking site for multiple effectors, namely PLCgamma, p85 proteins, GRB2, c-src and lck. Tyrosine 117-125 growth factor receptor bound protein 2 Homo sapiens 217-221 9175774-2 1997 Although the formation of Shc/Grb2 complexes involving Shc tyrosine residue 317 is necessary to induce this transformation, the Shc proteins in these Shc-overexpressing cells are not substantially tyrosine-phosphorylated. Tyrosine 59-67 growth factor receptor bound protein 2 Homo sapiens 30-34 9199344-2 1997 Previous work has shown that tyrosine-phosphorylated Shc forms complexes with another adapter protein, Grb2, and the Ras guanine nucleotide exchange factor SOS. Tyrosine 29-37 growth factor receptor bound protein 2 Homo sapiens 103-107 9148935-2 1997 Focal adhesion kinase (FAK) associates with integrin receptors, and FN-stimulated phosphorylation of FAK at Tyr-397 and Tyr-925 promotes the binding of Src family PTKs and Grb2, respectively. Tyrosine 120-123 growth factor receptor bound protein 2 Homo sapiens 172-176 9096689-11 1997 Taken together with all these findings, it is suggested that c-Src directly phosphorylates Shc on tyrosine residues, which in turn binds to Grb2 constitutively associated with Sos to form a Shc-Grb2-Sos complex, and that the complex formation is coupled with MAP kinase activation mediated by Ras activation in U937 cells. Tyrosine 98-106 growth factor receptor bound protein 2 Homo sapiens 140-144 9115214-1 1997 Previous work has demonstrated that SLP-76, a Grb2-associated tyrosine-phosphorylated protein, augments Interleukin-2 promoter activity when overexpressed in the Jurkat T cell line. Tyrosine 62-70 growth factor receptor bound protein 2 Homo sapiens 46-50 9108392-3 1997 These domains bind to proteins containing proline-rich regions or tyrosine-phosphorylated proteins and contribute to the association of Grb2/Ash and Shc with other signaling molecules. Tyrosine 66-74 growth factor receptor bound protein 2 Homo sapiens 136-140 9108392-3 1997 These domains bind to proteins containing proline-rich regions or tyrosine-phosphorylated proteins and contribute to the association of Grb2/Ash and Shc with other signaling molecules. Tyrosine 66-74 growth factor receptor bound protein 2 Homo sapiens 141-144 9096689-11 1997 Taken together with all these findings, it is suggested that c-Src directly phosphorylates Shc on tyrosine residues, which in turn binds to Grb2 constitutively associated with Sos to form a Shc-Grb2-Sos complex, and that the complex formation is coupled with MAP kinase activation mediated by Ras activation in U937 cells. Tyrosine 98-106 growth factor receptor bound protein 2 Homo sapiens 194-198 9079677-5 1997 Phosphopeptide competition and site-directed mutagenesis revealed that Tyr-1139 of erbB2 is the major binding site for the Grb7 SH2 domain, indicating an overlap in binding specificity between the Grb7 and Grb2 SH2 domains. Tyrosine 71-74 growth factor receptor bound protein 2 Homo sapiens 206-210 9209406-11 1997 Recently, we have shown that the proto-oncogene vav product (Vav) is also tyrosine-phosphorylated by treatment with GM-CSF and EPO and is constitutively associated with the SH3 domain of Grb2/Ash in UT-7. Tyrosine 74-82 growth factor receptor bound protein 2 Homo sapiens 192-195 9209406-4 1997 By means of the binding experiments using the GST fusion protein including the full length Grb2/Ash, we have found that Shc and unidentified 130-kDa and 135-kDa proteins are associated with Grb2/Ash and that they are tyrosine-phosphorylated by treatment with granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (EPO) in a human leukemia cell line UT-7. Tyrosine 217-225 growth factor receptor bound protein 2 Homo sapiens 91-95 9209406-4 1997 By means of the binding experiments using the GST fusion protein including the full length Grb2/Ash, we have found that Shc and unidentified 130-kDa and 135-kDa proteins are associated with Grb2/Ash and that they are tyrosine-phosphorylated by treatment with granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (EPO) in a human leukemia cell line UT-7. Tyrosine 217-225 growth factor receptor bound protein 2 Homo sapiens 195-198 9209406-11 1997 Recently, we have shown that the proto-oncogene vav product (Vav) is also tyrosine-phosphorylated by treatment with GM-CSF and EPO and is constitutively associated with the SH3 domain of Grb2/Ash in UT-7. Tyrosine 74-82 growth factor receptor bound protein 2 Homo sapiens 187-191 9113418-8 1997 Together, these results suggest that oxidants such as hydrogen peroxide stimulate tyrosine phosphorylation of receptor tyrosine kinases and these, in turn, mediate the down-stream signalling events including the recruitment of Grb2 by the receptor, activation of ERKs and induction of c-fos and c-jun expression. Tyrosine 82-90 growth factor receptor bound protein 2 Homo sapiens 227-231 9087451-3 1997 Since Grb2-Sos is a key regulator of the Ras signal transduction pathway, one plausible hypothesis has been that integrin-mediated tyrosine phosphorylation of FAK leads to activation of the Ras cascade and ultimately to mitogen activated protein (MAP) kinase activation. Tyrosine 131-139 growth factor receptor bound protein 2 Homo sapiens 6-10 9020117-7 1997 Tyr(P)992 receptors were associated with more SOS, Ras-GTPase activating protein, phosphatidylinositol 3-kinase, and SHPTP2/syp, but less Grb2, than receptors in the general population, and these receptors were more heavily phosphorylated than the general population of active receptors. Tyrosine 0-3 growth factor receptor bound protein 2 Homo sapiens 138-142 9113418-3 1997 In addition, induced tyrosine phosphorylation of FGFR1 by hydrogen peroxide resulted in complex formation with Grb2. Tyrosine 21-29 growth factor receptor bound protein 2 Homo sapiens 111-115 9344257-5 1997 This Ras-dependent MAP kinase activation requires tyrosine phosphorylation of "docking proteins," including the shc adapter protein, and depends upon recruitment of Grb2/Sos1 complexes to the plasma membrane, thus resembling the pathway of MAP kinase activation employed by the receptor tyrosine kinases. Tyrosine 50-58 growth factor receptor bound protein 2 Homo sapiens 165-169 9009162-8 1997 Also, the major tyrosine-phosphorylated proteins that associate with Grb2 in erbB2 over-expressing cancer cells appear to be erbB2 and Shc. Tyrosine 16-24 growth factor receptor bound protein 2 Homo sapiens 69-73 9016807-8 1997 Deletion mutants of GRB2 demonstrated that pp60c-src phosphorylated GRB2 on a tyrosine residue (residue 160) located between the SH2 domain and carboxyl terminal SH3 domain. Tyrosine 78-86 growth factor receptor bound protein 2 Homo sapiens 20-24 9016807-8 1997 Deletion mutants of GRB2 demonstrated that pp60c-src phosphorylated GRB2 on a tyrosine residue (residue 160) located between the SH2 domain and carboxyl terminal SH3 domain. Tyrosine 78-86 growth factor receptor bound protein 2 Homo sapiens 68-72 8955135-8 1996 Mutagenesis of BCR Tyr-177 to Phe completely abolished FES-induced BCR binding to the GRB2 SH2 domain, identifying Tyr-177 as an additional phosphorylation site for FES. Tyrosine 19-22 growth factor receptor bound protein 2 Homo sapiens 86-90 8940158-6 1996 Tyrosine phosphorylation of the beta3 integrin subunit facilitates association of Grb-2, an adaptor protein leading to activation of the Ras signaling pathway, and may contribute to the unique functional and signaling capabilities of alphavbeta3. Tyrosine 0-8 growth factor receptor bound protein 2 Homo sapiens 82-87 8955135-3 1996 Tyrosine phosphorylation led to the association of BCR with the RAS guanine nucleotide exchange complex GRB2-SOS in vivo via the GRB2 SH2 domain, linking BCR to RAS signaling (Maru, Y., Peters, K. L., Afar, D. E. H., Shibuya, M., Witte, O. N., and Smithgall, T. E. (1995) Mol. Tyrosine 0-8 growth factor receptor bound protein 2 Homo sapiens 104-108 8955135-3 1996 Tyrosine phosphorylation led to the association of BCR with the RAS guanine nucleotide exchange complex GRB2-SOS in vivo via the GRB2 SH2 domain, linking BCR to RAS signaling (Maru, Y., Peters, K. L., Afar, D. E. H., Shibuya, M., Witte, O. N., and Smithgall, T. E. (1995) Mol. Tyrosine 0-8 growth factor receptor bound protein 2 Homo sapiens 129-133 8943348-0 1996 Phosphorylation of tyrosine 720 in the platelet-derived growth factor alpha receptor is required for binding of Grb2 and SHP-2 but not for activation of Ras or cell proliferation. Tyrosine 19-27 growth factor receptor bound protein 2 Homo sapiens 112-116 8959326-0 1996 Multiple in vivo phosphorylated tyrosine phosphatase SHP-2 engages binding to Grb2 via tyrosine 584. Tyrosine 32-40 growth factor receptor bound protein 2 Homo sapiens 78-82 8959326-4 1996 Tyrosine 584 shares, together with tyrosine 546, the consensus sequence pY-X-N-X, a characteristic of potential binding sites for the SH2 domain of growth factor receptor-bound protein 2 (Grb2). Tyrosine 0-8 growth factor receptor bound protein 2 Homo sapiens 148-186 8959326-4 1996 Tyrosine 584 shares, together with tyrosine 546, the consensus sequence pY-X-N-X, a characteristic of potential binding sites for the SH2 domain of growth factor receptor-bound protein 2 (Grb2). Tyrosine 0-8 growth factor receptor bound protein 2 Homo sapiens 188-192 8959326-4 1996 Tyrosine 584 shares, together with tyrosine 546, the consensus sequence pY-X-N-X, a characteristic of potential binding sites for the SH2 domain of growth factor receptor-bound protein 2 (Grb2). Tyrosine 35-43 growth factor receptor bound protein 2 Homo sapiens 148-186 8959326-4 1996 Tyrosine 584 shares, together with tyrosine 546, the consensus sequence pY-X-N-X, a characteristic of potential binding sites for the SH2 domain of growth factor receptor-bound protein 2 (Grb2). Tyrosine 35-43 growth factor receptor bound protein 2 Homo sapiens 188-192 8959326-5 1996 We show here that mutation of tyrosine 584, but not tyrosine 546, to phenylalanine totally abolished the binding of Grb2 to SHP-2. Tyrosine 30-38 growth factor receptor bound protein 2 Homo sapiens 116-120 8986819-6 1996 In this study we show that L-selectin triggering of Jurkat cells using different antibodies or glycomimetics resulted in activation of the src-tyrosine kinase p56lck; tyrosine phosphorylation of intracellular proteins, in particular mitogen-activating protein kinase and L-selectin; and association of Grb2/Sos with L-selectin. Tyrosine 143-151 growth factor receptor bound protein 2 Homo sapiens 302-306 8943348-7 1996 SHP-2 bound the alphaPDGFR directly, whereas Grb2 associated indirectly, most probably via SHP-2, as Grb2 and SHP-2 coimmunoprecipitated when SHP-2 was tyrosine phosphorylated. Tyrosine 152-160 growth factor receptor bound protein 2 Homo sapiens 101-105 8943348-1 1996 Following binding of platelet-derived growth factor (PDGF), the PDGF alpha receptor (alphaPDGFR) becomes tyrosine phosphorylated and associates with a number of signal transduction molecules, including phospholipase Cgamma-1 (PLCgamma-1), phosphatidylinositol 3-kinase (PI3K), the phosphotyrosine phosphatase SHP-2, Grb2, and Src. Tyrosine 105-113 growth factor receptor bound protein 2 Homo sapiens 316-320 8810325-3 1996 Insulin stimulation resulted in co-immunoprecipitation of tyrosine-phosphorylated IRS1 with Grb2 and to a lesser extent CrkII. Tyrosine 58-66 growth factor receptor bound protein 2 Homo sapiens 92-96 8941336-5 1996 Previously identified Src sites include catalytic domain tyrosines-576 and -577, important for maximal FAK kinase activity, and tyrosine-925, which permits an SH2-mediated association with Grb2. Tyrosine 57-65 growth factor receptor bound protein 2 Homo sapiens 189-193 8950973-2 1996 In the present study we evaluated tyrosine phosphorylation of c-Cbl and the interaction of the Grb2/c-Cbl complex with signaling proteins upon activation of non-tyrosine (c-Mpl) and tyrosine kinase (c-Kit) receptors leading to myeloid cell proliferation. Tyrosine 161-169 growth factor receptor bound protein 2 Homo sapiens 95-99 8950973-10 1996 Taken together our results demonstrate that c-Cbl plays an important role in coupling both tyrosine and non-tyrosine kinase receptors to downstream effector molecules and that different signaling molecules interact with Grb2/c-Cbl complex when non-tyrosine or tyrosine kinase receptors are activated. Tyrosine 91-99 growth factor receptor bound protein 2 Homo sapiens 220-224 8824290-0 1996 Gastrin stimulates tyrosine phosphorylation of insulin receptor substrate 1 and its association with Grb2 and the phosphatidylinositol 3-kinase. Tyrosine 19-27 growth factor receptor bound protein 2 Homo sapiens 101-105 8824290-8 1996 We have previously reported that tyrosine phosphorylation of Shc and its association with the Grb2-Sos complex may contribute to the activation of the mitogen-activated protein kinase pathway by gastrin. Tyrosine 33-41 growth factor receptor bound protein 2 Homo sapiens 94-98 8824290-9 1996 We report here that Grb2 also interacts with tyrosine-phosphorylated IRS-1 in response to gastrin. Tyrosine 45-53 growth factor receptor bound protein 2 Homo sapiens 20-24 8934572-3 1996 The second tyrosine (from the membrane) of gp130, which was required for the tyrosine phosphorylation of SHP-2, its association with GRB2, and activation of a MAP kinase, was essential for mitogenesis, but not for anti-apoptosis. Tyrosine 11-19 growth factor receptor bound protein 2 Homo sapiens 133-137 8910327-6 1996 These results indicate that the binding of Grb2 to the phosphorylated Tyr-1068 of EGFR is crucial to the EGF-induced Ras/mitogen-activated protein kinase signaling pathway. Tyrosine 70-73 growth factor receptor bound protein 2 Homo sapiens 43-47 8810325-4 1996 Although Grb2 also associated with tyrosine-phosphorylated Shc, there was no detectable interaction of CrkII with Shc. Tyrosine 35-43 growth factor receptor bound protein 2 Homo sapiens 9-13 8810340-6 1996 Several derivatives of DeltaEGFR containing single, or multiple mutations at critical autophosphorylation sites were constructed and used to demonstrate that the major Shc binding site is Tyr-1148, and that Grb2 association occurs primarily through Tyr-1068. Tyrosine 249-252 growth factor receptor bound protein 2 Homo sapiens 207-211 8816475-5 1996 Using a tryptic phosphopeptide mapping approach, the in vivo phosphorylation of the Grb2 binding site on FAK (Tyr-925) was detected after fibronectin stimulation of NIH 3T3 cells and was constitutively phosphorylated in v-Src-transformed NIH 3T3 cells. Tyrosine 110-113 growth factor receptor bound protein 2 Homo sapiens 84-88 8816475-8 1996 Mutation of FAK Tyr-925 disrupted Grb2 binding, whereas mutation of the c-Src binding site on FAK (Tyr-397) disrupted both c-Src and Grb2 binding to FAK in vivo. Tyrosine 99-102 growth factor receptor bound protein 2 Homo sapiens 133-137 8816475-10 1996 Src-family binding and phosphorylation of FAK at Tyr-925 creates a Grb2 SH2-domain binding site and provides a link to the activation of the Ras signal transduction pathway. Tyrosine 49-52 growth factor receptor bound protein 2 Homo sapiens 67-71 8702728-8 1996 Following EGF or insulin stimulation, Shc is phosphorylated on single Tyr-317 residue serving as a docking site for Grb2. Tyrosine 70-73 growth factor receptor bound protein 2 Homo sapiens 116-120 8780727-0 1996 Suc1-associated neurotrophic factor target (SNT) protein is a major FGF-stimulated tyrosine phosphorylated 90-kDa protein which binds to the SH2 domain of GRB2. Tyrosine 83-91 growth factor receptor bound protein 2 Homo sapiens 155-159 8780727-3 1996 Tyrosine phosphorylated SNT binds to both p13suc1 protein and the SH2 domain of Grb2. Tyrosine 0-8 growth factor receptor bound protein 2 Homo sapiens 80-84 8780727-6 1996 Tyrosine phosphorylated SNT is localised in the plasma membrane where it could form a complex with Grb2 and Sos, enabling the initiation of a novel FGF-specific signalling pathway. Tyrosine 0-8 growth factor receptor bound protein 2 Homo sapiens 99-103 8866025-4 1996 The formation of Shc-Grb2 complex may directly link tyrosine phosphorylation events to Ras activation in TF-1 cells. Tyrosine 52-60 growth factor receptor bound protein 2 Homo sapiens 21-25 8765045-3 1996 The results reported here indicate that the resting, nonphosphorylated BCR associates with the Grb-2/Sos-linker SHC via the Ig-alpha immunoreceptor-based tyrosine activation motif (ITAM). Tyrosine 154-162 growth factor receptor bound protein 2 Homo sapiens 95-100 8765045-10 1996 In view of previous studies which demonstrated p21ras co-capping with ligated BCR, the data presented here suggest that Ig-alpha/beta- and SHC tyrosine phosphorylation-dependent recruitment of the Grb2/Sos complex to the receptor can occur and may provide a mechanism by which the nucleotide exchange activity of Sos could mediate activation of BCR-localized p21ras. Tyrosine 143-151 growth factor receptor bound protein 2 Homo sapiens 197-201 8663461-9 1996 Together, these data suggest the presence of distinct Grb2-SOS pools that are independently utilized by insulin and EGF in their recruitment to tyrosine-phosphorylated Shc. Tyrosine 144-152 growth factor receptor bound protein 2 Homo sapiens 54-58 8695800-5 1996 The SH3 domains of Grb2 form a stable complex with SOS1 and two proteins of 75 kD and 120 kD, which undergo tyrosine phosphorylation in Fc gamma RIIA stimulated cells. Tyrosine 108-116 growth factor receptor bound protein 2 Homo sapiens 19-23 8626530-5 1996 Tyrosine-phosphorylated Shc formed complexes with Grb2.Sos, and microinjection of anti-Shc antibody and Shc-SH2 GST fusion protein inhibited EGF stimulation of DNA synthesis in both cell lines. Tyrosine 0-8 growth factor receptor bound protein 2 Homo sapiens 50-54 8710377-0 1996 Formation of Shc/Grb2- and Crk adaptor complexes containing tyrosine phosphorylated Cbl upon stimulation of the B-cell antigen receptor. Tyrosine 60-68 growth factor receptor bound protein 2 Homo sapiens 17-21 8710377-1 1996 B-cell antigen receptor (BCR) stimulation induces tyrosine phosphorylation of the Shc adaptor protein and its association with Grb2. Tyrosine 50-58 growth factor receptor bound protein 2 Homo sapiens 127-131 8710377-3 1996 We reveal here an additional complexity of the BCR-induced Shc/Grb2 complex: it contains tyrosine phosphorylated proteins of 130, 110 and 75 kDa. Tyrosine 89-97 growth factor receptor bound protein 2 Homo sapiens 63-67 8752659-6 1996 Activation of these kinases is independent on protein and mRNA synthesis and is preceded by rapid tyrosine phosphorylation of an adaptor protein p66 (Shc) and formation of a complex between p66 Shc, a bridging molecule Grb2, and a Ras activator, mSos. Tyrosine 98-106 growth factor receptor bound protein 2 Homo sapiens 219-223 8649391-0 1996 Tyrosine phosphorylation of Grb2-associated proteins correlates with phospholipase C gamma 1 activation in T cells. Tyrosine 0-8 growth factor receptor bound protein 2 Homo sapiens 28-32 8649391-2 1996 We investigated the requirement for tyrosine phosphorylation of proteins which bind the Grb2 SH2 domain in TCR-mediated signal transduction by transfecting the Jurkat T-cell line with a cDNA encoding a chimeric protein designed to dephosphorylate these molecules. Tyrosine 36-44 growth factor receptor bound protein 2 Homo sapiens 88-92 8649391-6 1996 These data demonstrate that tyrosine phosphorylation of a protein(s) which binds the SH2 domain of Grb2 correlates with phospholipase C gamma 1 activation and suggest that such a phosphoprotein(s) plays a critical role in coupling the TCR with the phosphatidylinositol second-messenger pathway. Tyrosine 28-36 growth factor receptor bound protein 2 Homo sapiens 99-103 8662733-2 1996 We have previously demonstrated that a single tyrosine residue in the carboxyl terminus, Tyr489, is highly phosphorylated and is essential for efficient transformation of Fr3T3 fibroblasts by Tpr-Met and for the association of Tpr-Met with the Grb2 adaptor protein and phosphatidylinositol 3"-kinase. Tyrosine 46-54 growth factor receptor bound protein 2 Homo sapiens 244-248 8647288-6 1996 Furthermore, we observed association of ACK with an adaptor protein Grb2, which may suggest the involvement of Grb2 in EGF receptor-mediated tyrosine phosphorylation of ACK. Tyrosine 141-149 growth factor receptor bound protein 2 Homo sapiens 68-72 8647288-6 1996 Furthermore, we observed association of ACK with an adaptor protein Grb2, which may suggest the involvement of Grb2 in EGF receptor-mediated tyrosine phosphorylation of ACK. Tyrosine 141-149 growth factor receptor bound protein 2 Homo sapiens 111-115 8670205-0 1996 Tyrosine phosphorylation of a 94-kDa protein associated with GRB2/ASH is implicated in the signal transduction of hematopoietic survival factors. Tyrosine 0-8 growth factor receptor bound protein 2 Homo sapiens 61-65 8670205-0 1996 Tyrosine phosphorylation of a 94-kDa protein associated with GRB2/ASH is implicated in the signal transduction of hematopoietic survival factors. Tyrosine 0-8 growth factor receptor bound protein 2 Homo sapiens 66-69 8631894-9 1996 GRB2 binding occurred only when both tyrosine residues (Tyr-747 and Tyr-759) were phosphorylated. Tyrosine 37-45 growth factor receptor bound protein 2 Homo sapiens 0-4 8631894-9 1996 GRB2 binding occurred only when both tyrosine residues (Tyr-747 and Tyr-759) were phosphorylated. Tyrosine 56-59 growth factor receptor bound protein 2 Homo sapiens 0-4 8631894-9 1996 GRB2 binding occurred only when both tyrosine residues (Tyr-747 and Tyr-759) were phosphorylated. Tyrosine 68-71 growth factor receptor bound protein 2 Homo sapiens 0-4 8647120-8 1996 Our results indicate that SHPTP2 participates actively at an early stage in TCR signaling and that its phosphorylation on tyrosine may direct a Grb2-dependent association with selected substrates. Tyrosine 122-130 growth factor receptor bound protein 2 Homo sapiens 144-148 8622888-7 1996 HRG also induced the association of GRB2 with tyrosine phosphorylated p185c-erbB-2, p180erbB-4 and SHC. Tyrosine 46-54 growth factor receptor bound protein 2 Homo sapiens 36-40 8660324-6 1996 Furthermore, tyrosine phosphorylation of p52Shc and p46Shc and subsequent formation of Shc/Grb2 complex were detected in breast cancer cells in which the p185 tyrosine kinase is activated, indicating that p66Shc is not required for mediating the HER-2/neu signaling pathway in breast cancer cells. Tyrosine 13-21 growth factor receptor bound protein 2 Homo sapiens 91-95 8695788-10 1996 Analysis of tyrosine-phosphorylated RAFTK from adherent transfected COS cells showed that the Src homology 2 (SH2) domains of the Src and Fyn protein kinases as well as the Grb2 adaptor protein were able to specifically associate with RAFTK. Tyrosine 12-20 growth factor receptor bound protein 2 Homo sapiens 173-177 8662746-6 1996 FcgammaRI cross-linking induces the tyrosine phosphorylation of Shc; tyrosine-phosphorylated Shc binds to Grb2 forming a Shc-Grb2 complex. Tyrosine 36-44 growth factor receptor bound protein 2 Homo sapiens 106-110 8662746-6 1996 FcgammaRI cross-linking induces the tyrosine phosphorylation of Shc; tyrosine-phosphorylated Shc binds to Grb2 forming a Shc-Grb2 complex. Tyrosine 36-44 growth factor receptor bound protein 2 Homo sapiens 125-129 8662746-6 1996 FcgammaRI cross-linking induces the tyrosine phosphorylation of Shc; tyrosine-phosphorylated Shc binds to Grb2 forming a Shc-Grb2 complex. Tyrosine 69-77 growth factor receptor bound protein 2 Homo sapiens 106-110 8662746-6 1996 FcgammaRI cross-linking induces the tyrosine phosphorylation of Shc; tyrosine-phosphorylated Shc binds to Grb2 forming a Shc-Grb2 complex. Tyrosine 69-77 growth factor receptor bound protein 2 Homo sapiens 125-129 8639815-3 1996 We have recently shown that the SH2 containing tyrosine phosphatase, Syp, binds directly to both the tyrosine phosphorylated form of the Epo receptor (EpoR) and to Grb2 after Epo stimulation of M07e cells engineered to express high levels of human EpoRs (T. Tauchi, et al: J Biol Chem 270:5631, 1995). Tyrosine 47-55 growth factor receptor bound protein 2 Homo sapiens 164-168 8626404-6 1996 Investigation of the time course of Cbl dissociation from Grb2 reveals that it is transient and correlates with the kinetics of tyrosine phosphorylation of Cbl. Tyrosine 128-136 growth factor receptor bound protein 2 Homo sapiens 58-62 8666952-3 1996 Here we demonstrate formally that Grb2 associates with unphosphorylated SLP-76 and map the Grb2 binding site on SLP-76 undergoes rapid tyrosine phosphorylation and associates with tyrosine phosphoproteins of 36, 62, and 130 kD. Tyrosine 135-143 growth factor receptor bound protein 2 Homo sapiens 34-38 8666952-3 1996 Here we demonstrate formally that Grb2 associates with unphosphorylated SLP-76 and map the Grb2 binding site on SLP-76 undergoes rapid tyrosine phosphorylation and associates with tyrosine phosphoproteins of 36, 62, and 130 kD. Tyrosine 135-143 growth factor receptor bound protein 2 Homo sapiens 91-95 8621421-3 1996 The data revealed new potential Grb2 binding sites at Tyr-1114 (epidermal growth factor receptor (EGFR) C-tail); Tyr-743 (platelet-derived growth factor receptor (PDGFR) insert region), Tyr-1110 from the E-helix of the catalytic domain of insulin receptor (IR), and Tyr-47, Tyr-939, and Tyr-727 in IRS-1. Tyrosine 54-57 growth factor receptor bound protein 2 Homo sapiens 32-36 8621421-3 1996 The data revealed new potential Grb2 binding sites at Tyr-1114 (epidermal growth factor receptor (EGFR) C-tail); Tyr-743 (platelet-derived growth factor receptor (PDGFR) insert region), Tyr-1110 from the E-helix of the catalytic domain of insulin receptor (IR), and Tyr-47, Tyr-939, and Tyr-727 in IRS-1. Tyrosine 113-116 growth factor receptor bound protein 2 Homo sapiens 32-36 8621421-5 1996 Tyr-1068 and -1086 from the C-tail of EGFR, Tyr-684 from the kinase insert region of PDGFR, and Tyr-895 from IRS-1 were confirmed as major binding sites for the Grb2 SH2 domain. Tyrosine 44-47 growth factor receptor bound protein 2 Homo sapiens 161-165 8621421-5 1996 Tyr-1068 and -1086 from the C-tail of EGFR, Tyr-684 from the kinase insert region of PDGFR, and Tyr-895 from IRS-1 were confirmed as major binding sites for the Grb2 SH2 domain. Tyrosine 44-47 growth factor receptor bound protein 2 Homo sapiens 161-165 8621421-3 1996 The data revealed new potential Grb2 binding sites at Tyr-1114 (epidermal growth factor receptor (EGFR) C-tail); Tyr-743 (platelet-derived growth factor receptor (PDGFR) insert region), Tyr-1110 from the E-helix of the catalytic domain of insulin receptor (IR), and Tyr-47, Tyr-939, and Tyr-727 in IRS-1. Tyrosine 113-116 growth factor receptor bound protein 2 Homo sapiens 32-36 8621421-3 1996 The data revealed new potential Grb2 binding sites at Tyr-1114 (epidermal growth factor receptor (EGFR) C-tail); Tyr-743 (platelet-derived growth factor receptor (PDGFR) insert region), Tyr-1110 from the E-helix of the catalytic domain of insulin receptor (IR), and Tyr-47, Tyr-939, and Tyr-727 in IRS-1. Tyrosine 113-116 growth factor receptor bound protein 2 Homo sapiens 32-36 8621421-3 1996 The data revealed new potential Grb2 binding sites at Tyr-1114 (epidermal growth factor receptor (EGFR) C-tail); Tyr-743 (platelet-derived growth factor receptor (PDGFR) insert region), Tyr-1110 from the E-helix of the catalytic domain of insulin receptor (IR), and Tyr-47, Tyr-939, and Tyr-727 in IRS-1. Tyrosine 113-116 growth factor receptor bound protein 2 Homo sapiens 32-36 8621421-3 1996 The data revealed new potential Grb2 binding sites at Tyr-1114 (epidermal growth factor receptor (EGFR) C-tail); Tyr-743 (platelet-derived growth factor receptor (PDGFR) insert region), Tyr-1110 from the E-helix of the catalytic domain of insulin receptor (IR), and Tyr-47, Tyr-939, and Tyr-727 in IRS-1. Tyrosine 113-116 growth factor receptor bound protein 2 Homo sapiens 32-36 8621421-5 1996 Tyr-1068 and -1086 from the C-tail of EGFR, Tyr-684 from the kinase insert region of PDGFR, and Tyr-895 from IRS-1 were confirmed as major binding sites for the Grb2 SH2 domain. Tyrosine 0-3 growth factor receptor bound protein 2 Homo sapiens 161-165 8577724-3 1996 In response to calcium influx, Shc, Grb2, and Sos1 inducibly associate with a 180-kDa tyrosine-phosphorylated protein, which was determined to be the epidermal growth factor receptor (EGFR). Tyrosine 86-94 growth factor receptor bound protein 2 Homo sapiens 36-40 8621719-7 1996 Tyrosine-phosphorylated Shc, which prominently associated with Grb2, was detected in association with Cbl in activated B cells. Tyrosine 0-8 growth factor receptor bound protein 2 Homo sapiens 63-67 8621719-8 1996 Thus, Grb2 and Shc adaptors, which associate with immunoreceptor tyrosine based activation motifs, may link Cbl to the B cell receptor. Tyrosine 65-73 growth factor receptor bound protein 2 Homo sapiens 6-10 8617726-7 1996 The unique non-phosphotyrosine-mediated binding of Shc may allow direct tyrosine phosphorylation of Shc by v-Abl and subsequent activation of the Ras pathway through assembly of a signaling complex with Grb2-mSos. Tyrosine 22-30 growth factor receptor bound protein 2 Homo sapiens 203-207 8549807-0 1996 Gastrin induces tyrosine phosphorylation of Shc proteins and their association with the Grb2/Sos complex. Tyrosine 16-24 growth factor receptor bound protein 2 Homo sapiens 88-92 8549807-8 1996 Tyrosine phosphorylation of Shc and subsequent complex formation with Grb2 and Sos appear to be a common mechanism by which tyrosine kinase receptors and the G/CCKB G protein-coupled receptor stimulate the Ras-dependent MAP kinase pathway. Tyrosine 0-8 growth factor receptor bound protein 2 Homo sapiens 70-74 8677749-4 1996 Here we report that granulocyte/macrophage-colony- stimulating factor (GM-CSF), interleukin-3, and erythropoietin (Epo) induce rapid and transient tyrosine phosphorylation of Vav and that Vav is constitutively associated with the SH3 domain of Grb2/Ash in a human leukemia cell line UT-7. Tyrosine 147-155 growth factor receptor bound protein 2 Homo sapiens 244-248 8677749-4 1996 Here we report that granulocyte/macrophage-colony- stimulating factor (GM-CSF), interleukin-3, and erythropoietin (Epo) induce rapid and transient tyrosine phosphorylation of Vav and that Vav is constitutively associated with the SH3 domain of Grb2/Ash in a human leukemia cell line UT-7. Tyrosine 147-155 growth factor receptor bound protein 2 Homo sapiens 249-252 8677749-6 1996 Furthermore, we have shown that the proto-oncogene c-cbl product (c-Cbl) is also tyrosine-phosphorylated by stimulation with GM-CSF or Epo and is constitutively associated with the SH3 domain of Grb2/Ash in UT-7. Tyrosine 81-89 growth factor receptor bound protein 2 Homo sapiens 195-199 8677749-6 1996 Furthermore, we have shown that the proto-oncogene c-cbl product (c-Cbl) is also tyrosine-phosphorylated by stimulation with GM-CSF or Epo and is constitutively associated with the SH3 domain of Grb2/Ash in UT-7. Tyrosine 81-89 growth factor receptor bound protein 2 Homo sapiens 200-203 7492780-3 1995 The tyrosine-phosphorylated 170-kD substrate strongly associated with the 85-kD subunit of phosphoinositol-3 (PI-3) kinase and with Grb-2. Tyrosine 4-12 growth factor receptor bound protein 2 Homo sapiens 132-137 8547634-0 1996 Specific involvement of tyrosine 764 of human granulocyte colony-stimulating factor receptor in signal transduction mediated by p145/Shc/GRB2 or p90/GRB2 complexes. Tyrosine 24-32 growth factor receptor bound protein 2 Homo sapiens 137-141 8547634-0 1996 Specific involvement of tyrosine 764 of human granulocyte colony-stimulating factor receptor in signal transduction mediated by p145/Shc/GRB2 or p90/GRB2 complexes. Tyrosine 24-32 growth factor receptor bound protein 2 Homo sapiens 149-153 7486658-0 1995 A 115 kDa tyrosine phosphorylated protein associates with Grb-2 in activated Jurkat cells. Tyrosine 10-18 growth factor receptor bound protein 2 Homo sapiens 58-63 8536716-1 1995 The adaptor molecule growth-factor-receptor-bound protein-2 (Grb2) plays a role in insulin action since it links tyrosine phosphorylated IRS-1 and Shc to the guanine-nucleotide-exchange factor, Sos, which initiates the mitogen-activated-protein (MAP) kinase cascade by producing Ras-GTP. Tyrosine 113-121 growth factor receptor bound protein 2 Homo sapiens 21-59 8536716-1 1995 The adaptor molecule growth-factor-receptor-bound protein-2 (Grb2) plays a role in insulin action since it links tyrosine phosphorylated IRS-1 and Shc to the guanine-nucleotide-exchange factor, Sos, which initiates the mitogen-activated-protein (MAP) kinase cascade by producing Ras-GTP. Tyrosine 113-121 growth factor receptor bound protein 2 Homo sapiens 61-65 7500025-7 1995 The SH2 domain of Grb2 is directly associated with tyrosine-phosphorylated JAK2. Tyrosine 51-59 growth factor receptor bound protein 2 Homo sapiens 18-22 7561087-2 1995 To molecularly characterize receptor-activated proximal signaling events, tyrosine-phosphorylated proteins co-precipitating with a Grb2 fusion protein after receptor activation were analyzed. Tyrosine 74-82 growth factor receptor bound protein 2 Homo sapiens 131-135 7561087-3 1995 Ligation of CD28, but not other costimulatory molecules, induced the tyrosine phosphorylation of two previously identified Grb2 binding proteins (pp76 and pp116). Tyrosine 69-77 growth factor receptor bound protein 2 Homo sapiens 123-127 7561087-4 1995 A third Grb2 binding protein (pp36) was extensively tyrosine phosphophorylated in response to combined CD3 and CD28 activation, but not in response to ligation of either receptor alone. Tyrosine 52-60 growth factor receptor bound protein 2 Homo sapiens 8-12 7561087-5 1995 cAMP and co-ligation of CD45 affected the receptor-activated tyrosine phosphorylation of Grb2-associated proteins. Tyrosine 61-69 growth factor receptor bound protein 2 Homo sapiens 89-93 7478553-1 1995 Formation of a complex of the nucleotide exchange factor Sos, the SH2 and SH3 containing adaptor protein Grb2/Sem-5 and tyrosine phosphorylated EGF receptor and Shc has been implicated in the activation of Ras by epidermal growth factor (EGF) in fibroblasts: related mechanisms for activation of Ras operate in other cell types. Tyrosine 120-128 growth factor receptor bound protein 2 Homo sapiens 105-109 7478553-4 1995 This modification of Sos does not alter its ability to bind Grb2, but correlates with strong inhibition of the binding of the Sos/Grb2 complex to tyrosine phosphorylated sequences, either a tyrosine phosphopeptide in cell lysates or p36 in intact cells. Tyrosine 146-154 growth factor receptor bound protein 2 Homo sapiens 130-134 7478553-4 1995 This modification of Sos does not alter its ability to bind Grb2, but correlates with strong inhibition of the binding of the Sos/Grb2 complex to tyrosine phosphorylated sequences, either a tyrosine phosphopeptide in cell lysates or p36 in intact cells. Tyrosine 190-198 growth factor receptor bound protein 2 Homo sapiens 130-134 8536716-4 1995 In fibroblasts over-expressing insulin receptors we observed that two tyrosine-phosphorylated proteins interact with Grb2 and with a mutant of Grb2, which lacks the Src homology 2 (SH2) domain, indicating that these proteins associate with the SH3 domains of Grb2. Tyrosine 70-78 growth factor receptor bound protein 2 Homo sapiens 117-121 8536716-4 1995 In fibroblasts over-expressing insulin receptors we observed that two tyrosine-phosphorylated proteins interact with Grb2 and with a mutant of Grb2, which lacks the Src homology 2 (SH2) domain, indicating that these proteins associate with the SH3 domains of Grb2. Tyrosine 70-78 growth factor receptor bound protein 2 Homo sapiens 143-147 8536716-4 1995 In fibroblasts over-expressing insulin receptors we observed that two tyrosine-phosphorylated proteins interact with Grb2 and with a mutant of Grb2, which lacks the Src homology 2 (SH2) domain, indicating that these proteins associate with the SH3 domains of Grb2. Tyrosine 70-78 growth factor receptor bound protein 2 Homo sapiens 143-147 8524249-9 1995 This finding suggests that in Abl-transformed cells, more than one class of tyrosine-phosphorylated sites (those that bind the Grb2 SH2 domain and those that bind the Crk SH2 domain) can lead to Ras activation. Tyrosine 76-84 growth factor receptor bound protein 2 Homo sapiens 127-131 7559490-6 1995 Another pool of Grb2 was found in complex with a tyrosine-phosphorylated 89-kDa component after FGF-2 stimulation. Tyrosine 49-57 growth factor receptor bound protein 2 Homo sapiens 16-20 7559490-9 1995 Tyrosine-phosphorylated p89 was found exclusively in the membrane fraction, indicating its role in bringing Grb2, as well as Sos, to the plasma membrane. Tyrosine 0-8 growth factor receptor bound protein 2 Homo sapiens 108-112 7568038-4 1995 The requirement for tyrosine phosphorylation of the Tyr-Met-Asn-Met motif for SH2 domain binding implicates an intervening protein-tyrosine kinase in the recruitment of PI 3-kinase and GRB-2 by CD28. Tyrosine 20-28 growth factor receptor bound protein 2 Homo sapiens 185-190 7568038-4 1995 The requirement for tyrosine phosphorylation of the Tyr-Met-Asn-Met motif for SH2 domain binding implicates an intervening protein-tyrosine kinase in the recruitment of PI 3-kinase and GRB-2 by CD28. Tyrosine 52-55 growth factor receptor bound protein 2 Homo sapiens 185-190 7549895-5 1995 IRS-1 and 4PS possess a number of tyrosine phosphorylation sites that are within motifs that bind specific SH2-containing molecules known to be involved in mitogenic signaling such as PI-3 kinase, SHPTP-2 (Syp) and Grb-2. Tyrosine 34-42 growth factor receptor bound protein 2 Homo sapiens 215-220 7651538-3 1995 RTK-mediated mitogenic signalling involves a series of SH2- and SH3-dependent protein-protein interactions between tyrosine-phosphorylated receptor, Shc, Grb2 and Sos, resulting in Ras-dependent MAP kinase activation. Tyrosine 115-123 growth factor receptor bound protein 2 Homo sapiens 154-158 7651538-5 1995 Here we demonstrate that activation of MAP kinase by Gi-coupled receptors is preceded by the G beta gamma-mediated tyrosine phosphorylation of Shc, leading to an increased functional association between Shc, Grb2 and Sos. Tyrosine 115-123 growth factor receptor bound protein 2 Homo sapiens 208-212 7664271-3 1995 In the present studies using human MCF-7 breast cancer cells, we show that tyrosine phosphorylated DF3 directly interacts with the SH2 domain of the adaptor protein Grb2. Tyrosine 75-83 growth factor receptor bound protein 2 Homo sapiens 165-169 7795229-7 1995 The tyrosine phosphorylation of Jak2 was accompanied by increased kinase activity, whereas Shc tyrosine phosphorylation induced its association with a 25-kD protein, Grb2. Tyrosine 95-103 growth factor receptor bound protein 2 Homo sapiens 166-170 7541031-5 1995 In comparison, activation of Jurkat cells with a T cell receptor agonist monoclonal antibody resulted in the co-immunoprecipitation of a 120-kDa tyrosine-phosphorylated protein with Grb2 and a 105-kDa protein with SHPTP2. Tyrosine 145-153 growth factor receptor bound protein 2 Homo sapiens 182-186 7539794-4 1995 Shc is tyrosine phosphorylated in antigen receptor-activated T cells and can potentially form a complex with the adapter molecule Grb2 and could thus recruit the Ras guanine nucleotide exchange protein Sos into the antigen receptor complex. Tyrosine 7-15 growth factor receptor bound protein 2 Homo sapiens 130-134 7597091-3 1995 The results demonstrate that tyrosine-phosphorylated pp125FAK directly interacts with the SH2 domain of Grb2. Tyrosine 29-37 growth factor receptor bound protein 2 Homo sapiens 104-108 7539782-0 1995 Tyrosine phosphorylation of the proto-oncogene product Vav and its association with the adapter Grb2/Ash in a human leukemia cell line UT-7. Tyrosine 0-8 growth factor receptor bound protein 2 Homo sapiens 96-100 7759503-3 1995 Stimulation of smooth muscle cells with angiotensin II resulted in tyrosine phosphorylation on Shc proteins and subsequent complex formation between Shc and growth factor receptor binding protein-2 (GRB2). Tyrosine 67-75 growth factor receptor bound protein 2 Homo sapiens 157-197 7537740-7 1995 By means of the binding experiments using the glutathione S-transferase fusion protein including the full-length Grb2/Ash, we have found that Shc and unidentified 130- and 135-kDa proteins are associated with Grb2/Ash and that they are tyrosine phosphorylated by treatment with GM-CSF or Epo in a human leukemia cell line, UT-7. Tyrosine 236-244 growth factor receptor bound protein 2 Homo sapiens 113-117 7737969-4 1995 Tyrosine-phosphorylated PI 3-kinase interacts with the SH2 domain of Grb2. Tyrosine 0-8 growth factor receptor bound protein 2 Homo sapiens 69-73 7537265-4 1995 Mitotic, tyrosine-phosphorylated Sam 68 bound selectively to recombinant SH2 domains with significantly different affinities (c-Src approximately Ras GTPase activating protein > p85 alpha (amino-terminal) > Grb2 >> p85 alpha (COOH-terminal)). Tyrosine 9-17 growth factor receptor bound protein 2 Homo sapiens 213-217 7539782-0 1995 Tyrosine phosphorylation of the proto-oncogene product Vav and its association with the adapter Grb2/Ash in a human leukemia cell line UT-7. Tyrosine 0-8 growth factor receptor bound protein 2 Homo sapiens 101-104 7896829-5 1995 Tyrosine phosphorylation of Shc and its association with Grb2 were profoundly reduced in both Lyn- and Syk-deficient B cells upon BCR stimulation. Tyrosine 0-8 growth factor receptor bound protein 2 Homo sapiens 57-61 7970705-7 1994 We find that all these mutant receptors can induce tyrosine phosphorylation of Shc which then acts as a binding site for the Grb2/Sos signaling complex. Tyrosine 51-59 growth factor receptor bound protein 2 Homo sapiens 125-129 7529874-0 1995 Tyrosine phosphorylation of BCR by FPS/FES protein-tyrosine kinases induces association of BCR with GRB-2/SOS. Tyrosine 0-8 growth factor receptor bound protein 2 Homo sapiens 100-105 7529874-6 1995 Tyrosine phosphorylation of BCR in v-fps-transformed cells induced its association with GRB-2/SOS, the RAS guanine nucleotide exchange factor complex. Tyrosine 0-8 growth factor receptor bound protein 2 Homo sapiens 88-93 7527043-0 1994 Grb2/Ash binds directly to tyrosines 1068 and 1086 and indirectly to tyrosine 1148 of activated human epidermal growth factor receptors in intact cells. Tyrosine 27-36 growth factor receptor bound protein 2 Homo sapiens 0-4 7527043-0 1994 Grb2/Ash binds directly to tyrosines 1068 and 1086 and indirectly to tyrosine 1148 of activated human epidermal growth factor receptors in intact cells. Tyrosine 27-36 growth factor receptor bound protein 2 Homo sapiens 5-8 7527043-0 1994 Grb2/Ash binds directly to tyrosines 1068 and 1086 and indirectly to tyrosine 1148 of activated human epidermal growth factor receptors in intact cells. Tyrosine 27-35 growth factor receptor bound protein 2 Homo sapiens 0-4 7527043-0 1994 Grb2/Ash binds directly to tyrosines 1068 and 1086 and indirectly to tyrosine 1148 of activated human epidermal growth factor receptors in intact cells. Tyrosine 27-35 growth factor receptor bound protein 2 Homo sapiens 5-8 7527043-3 1994 In intact cells, the amount of Grb2/Ash coimmunoprecipitated with mutant receptors retaining tyrosines 992, 1068, 1086, 1148, or 1173 was approximately 10, 85, 55, 50, or 20% of wild-type levels, respectively. Tyrosine 93-102 growth factor receptor bound protein 2 Homo sapiens 31-35 7527043-3 1994 In intact cells, the amount of Grb2/Ash coimmunoprecipitated with mutant receptors retaining tyrosines 992, 1068, 1086, 1148, or 1173 was approximately 10, 85, 55, 50, or 20% of wild-type levels, respectively. Tyrosine 93-102 growth factor receptor bound protein 2 Homo sapiens 36-39 7527043-4 1994 The association of Grb2/Ash with in vitro autophosphorylated EGF receptor mutants was detectable in those retaining either tyrosines 1068 or 1086 but not in other mutants including those retaining tyrosine 1148. Tyrosine 123-132 growth factor receptor bound protein 2 Homo sapiens 19-23 7527043-4 1994 The association of Grb2/Ash with in vitro autophosphorylated EGF receptor mutants was detectable in those retaining either tyrosines 1068 or 1086 but not in other mutants including those retaining tyrosine 1148. Tyrosine 123-132 growth factor receptor bound protein 2 Homo sapiens 24-27 7527043-4 1994 The association of Grb2/Ash with in vitro autophosphorylated EGF receptor mutants was detectable in those retaining either tyrosines 1068 or 1086 but not in other mutants including those retaining tyrosine 1148. Tyrosine 123-131 growth factor receptor bound protein 2 Homo sapiens 19-23 7527043-4 1994 The association of Grb2/Ash with in vitro autophosphorylated EGF receptor mutants was detectable in those retaining either tyrosines 1068 or 1086 but not in other mutants including those retaining tyrosine 1148. Tyrosine 123-131 growth factor receptor bound protein 2 Homo sapiens 24-27 7527043-5 1994 In peptide inhibition assay, phosphorylated peptides representing tyrosines 1068 and 1086 inhibited the binding of Grb2/Ash to in vitro autophosphorylated wild-type EGF receptors, whereas the other peptides representing tyrosines 992, 1148, and 1173 failed to inhibit the binding. Tyrosine 66-75 growth factor receptor bound protein 2 Homo sapiens 115-119 7527043-5 1994 In peptide inhibition assay, phosphorylated peptides representing tyrosines 1068 and 1086 inhibited the binding of Grb2/Ash to in vitro autophosphorylated wild-type EGF receptors, whereas the other peptides representing tyrosines 992, 1148, and 1173 failed to inhibit the binding. Tyrosine 66-75 growth factor receptor bound protein 2 Homo sapiens 120-123 7527043-5 1994 In peptide inhibition assay, phosphorylated peptides representing tyrosines 1068 and 1086 inhibited the binding of Grb2/Ash to in vitro autophosphorylated wild-type EGF receptors, whereas the other peptides representing tyrosines 992, 1148, and 1173 failed to inhibit the binding. Tyrosine 220-229 growth factor receptor bound protein 2 Homo sapiens 115-119 7527043-5 1994 In peptide inhibition assay, phosphorylated peptides representing tyrosines 1068 and 1086 inhibited the binding of Grb2/Ash to in vitro autophosphorylated wild-type EGF receptors, whereas the other peptides representing tyrosines 992, 1148, and 1173 failed to inhibit the binding. Tyrosine 220-229 growth factor receptor bound protein 2 Homo sapiens 120-123 7527043-8 1994 269, 18674-18678), these results indicate that tyrosines 1068 and 1086 of activated human EGF receptors are direct high affinity binding sites of Grb2/Ash and that tyrosine 1148 is an indirect binding site through Shc in intact cells. Tyrosine 47-56 growth factor receptor bound protein 2 Homo sapiens 146-150 7527043-8 1994 269, 18674-18678), these results indicate that tyrosines 1068 and 1086 of activated human EGF receptors are direct high affinity binding sites of Grb2/Ash and that tyrosine 1148 is an indirect binding site through Shc in intact cells. Tyrosine 47-56 growth factor receptor bound protein 2 Homo sapiens 151-154 7527043-8 1994 269, 18674-18678), these results indicate that tyrosines 1068 and 1086 of activated human EGF receptors are direct high affinity binding sites of Grb2/Ash and that tyrosine 1148 is an indirect binding site through Shc in intact cells. Tyrosine 47-55 growth factor receptor bound protein 2 Homo sapiens 146-150 7527043-8 1994 269, 18674-18678), these results indicate that tyrosines 1068 and 1086 of activated human EGF receptors are direct high affinity binding sites of Grb2/Ash and that tyrosine 1148 is an indirect binding site through Shc in intact cells. Tyrosine 47-55 growth factor receptor bound protein 2 Homo sapiens 151-154 7893993-7 1994 After growth factor stimulation, the tyrosine phosphorylated EGF receptor binds the Grb2/Sos complex, translocating it to the plasma membrane. Tyrosine 37-45 growth factor receptor bound protein 2 Homo sapiens 84-88 7893993-9 1994 In contrast, the insulin receptor does not bind Grb2 directly but rather induces the tyrosine phosphorylation of two proteins, insulin receptor substrate-1 and Shc, that bind the Grb2/Sos complex. Tyrosine 85-93 growth factor receptor bound protein 2 Homo sapiens 179-183 7806540-7 1994 Cell lines expressing mutant Y1158,Y1162F,Y1163F (YFF) receptors showed insulin-induced tyrosine phosphorylation of Shc, Shc.Grb2 complex formation, and p21ras-GTP formation, whereas tyrosine phosphorylation of IRS1 was strongly decreased and formation of IRS1.Grb2 complexes was undetectable. Tyrosine 88-96 growth factor receptor bound protein 2 Homo sapiens 125-129 7806540-7 1994 Cell lines expressing mutant Y1158,Y1162F,Y1163F (YFF) receptors showed insulin-induced tyrosine phosphorylation of Shc, Shc.Grb2 complex formation, and p21ras-GTP formation, whereas tyrosine phosphorylation of IRS1 was strongly decreased and formation of IRS1.Grb2 complexes was undetectable. Tyrosine 88-96 growth factor receptor bound protein 2 Homo sapiens 261-265 7961995-5 1994 In an interleukin (IL)-3-dependent cell line expressing the transfected wild-type EpoR, Epo, or IL-3 induced tyrosine phosphorylation of Shc and its association with Grb2. Tyrosine 109-117 growth factor receptor bound protein 2 Homo sapiens 166-170 7961995-10 1994 These results suggest that the carboxyl-terminal region of EpoR may play a crucial role in activation of MAP kinases through the Ras signaling pathway which may be activated by tyrosine phosphorylation of Shc and its association with Grb2. Tyrosine 177-185 growth factor receptor bound protein 2 Homo sapiens 234-238 7525306-2 1994 Following tyrosine phosphorylation by either receptor or non-receptor tyrosine kinases, Shc may interact with the adaptor protein Grb2, which is linked to Sos1, a guanine nucleotide exchange factor for human ras. Tyrosine 10-18 growth factor receptor bound protein 2 Homo sapiens 130-134 7523381-6 1994 Furthermore, Syp became marginally phosphorylated on tyrosine upon c-kit receptor activation, and tyrosine-phosphorylated Syp was found to be complexed with Grb2 in steel factor-stimulated M07e cells. Tyrosine 98-106 growth factor receptor bound protein 2 Homo sapiens 157-161 8051109-9 1994 In a specific response to B cell activation, the Shc-Grb2 complex associates with several tyrosine-phosphorylated proteins, including two prominent phosphoproteins with molecular masses of 130 and 110 kDa. Tyrosine 90-98 growth factor receptor bound protein 2 Homo sapiens 53-57 7522233-3 1994 The Src homology 2 (SH2) domain of the adaptor protein Grb2 bound with high affinity to tyrosine-phosphorylated SHPTP2 following treatment of cells with IL-3 or GM-CSF, but not IL-4. Tyrosine 88-96 growth factor receptor bound protein 2 Homo sapiens 55-59 7929159-8 1994 These results demonstrate that tyrosine-phosphorylated Shc specifically interacts with the SH2 domain of Grb2. Tyrosine 31-39 growth factor receptor bound protein 2 Homo sapiens 105-109 7935391-0 1994 Tyr-716 in the platelet-derived growth factor beta-receptor kinase insert is involved in GRB2 binding and Ras activation. Tyrosine 0-3 growth factor receptor bound protein 2 Homo sapiens 89-93 7935391-4 1994 Here we show that Tyr-716, a novel autophosphorylation site in the PDGF beta-receptor kinase insert, mediates direct binding of GRB2 in vitro and in vivo. Tyrosine 18-21 growth factor receptor bound protein 2 Homo sapiens 128-132 7935391-6 1994 Furthermore, a synthetic phosphorylated peptide containing Tyr-716 bound GRB2, and this peptide specifically interrupted the interaction between GRB2 and the wild-type receptor. Tyrosine 59-62 growth factor receptor bound protein 2 Homo sapiens 73-77 7935391-6 1994 Furthermore, a synthetic phosphorylated peptide containing Tyr-716 bound GRB2, and this peptide specifically interrupted the interaction between GRB2 and the wild-type receptor. Tyrosine 59-62 growth factor receptor bound protein 2 Homo sapiens 145-149 8051109-0 1994 B cell antigen receptor stimulation induces formation of a Shc-Grb2 complex containing multiple tyrosine-phosphorylated proteins. Tyrosine 96-104 growth factor receptor bound protein 2 Homo sapiens 63-67 7518560-4 1994 These findings were confirmed by using a dephosphorylation protection assay and by measuring the dissociation constants of Grb2"s SH2 domain to tyrosine-phosphorylated peptides, using real-time biospecific interaction analysis (BIAcore). Tyrosine 144-152 growth factor receptor bound protein 2 Homo sapiens 123-127 8051109-1 1994 Activation of growth factor receptor tyrosine kinases, such as the epidermal growth factor and insulin receptors, induces tyrosine phosphorylation of Shc proteins and their association with the SH2 domain-containing adaptor protein Grb2. Tyrosine 37-45 growth factor receptor bound protein 2 Homo sapiens 232-236 7518560-9 1994 These analyses reveal a hierarchy of interactions between Grb2 and Shc with the EGFR and indicate that Grb2 can bind the tyrosine-phosphorylated EGFR directly, as well as indirectly via Shc. Tyrosine 121-129 growth factor receptor bound protein 2 Homo sapiens 103-107 7518443-0 1994 Receptor tyrosine phosphatase R-PTP-alpha is tyrosine-phosphorylated and associated with the adaptor protein Grb2. Tyrosine 9-17 growth factor receptor bound protein 2 Homo sapiens 109-113 7518443-3 1994 We report that a ubiquitous R-PTPase, R-PTP-alpha, is tyrosine-phosphorylated and associated in vivo with the Grb2 protein. Tyrosine 54-62 growth factor receptor bound protein 2 Homo sapiens 110-114 8208538-2 1994 In this study we examine the ability of tyrosine phosphorylated proteins from Jurkat T cells stimulated by CD2 or T cell receptor-CD3 to interact with the src homology 2 or src homology 3 domains from eight different proteins involved in signal transduction in lymphocytes: Vav, Shc, Nck, phosphatidylinositol-3-kinase, phospholipase C-gamma 1, Ras-GTPase activating protein, c-Crk and Grb2. Tyrosine 40-48 growth factor receptor bound protein 2 Homo sapiens 386-390 8195171-8 1994 Tyrosine-phosphorylated Shc, in turn, formed a complex with the signaling molecule Grb2. Tyrosine 0-8 growth factor receptor bound protein 2 Homo sapiens 83-87 8119884-6 1994 Tyrosine-phosphorylated Shc was found to be capable of associating with the SH2 domain of Grb2 following IL-2 stimulation. Tyrosine 0-8 growth factor receptor bound protein 2 Homo sapiens 90-94 8144662-5 1994 Thus, the kinetics of Grb2 association with IRS-1 and She corresponded closely to the time course of tyrosine phosphorylation of IRS-1 and Shc, respectively. Tyrosine 101-109 growth factor receptor bound protein 2 Homo sapiens 22-26 8119884-7 1994 These results indicate that tyrosine phosphorylation of Shc and its association with Grb2 may be important events in IL-2-initiated signal transduction events in T cells. Tyrosine 28-36 growth factor receptor bound protein 2 Homo sapiens 85-89 8112292-5 1994 Grb2 associates with tyrosine phosphorylated proteins through its SH2 domain, and with the Ras guanine nucleotide releasing protein mSos1 through its SH3 domains. Tyrosine 21-29 growth factor receptor bound protein 2 Homo sapiens 0-4 8112292-8 1994 In vitro, the Grb2 SH2 domain bound Bcr-Abl through recognition of a tyrosine phosphorylation site within the amino-terminal bcr-encoded sequence (p.Tyr177-Val-Asn-Val), that is common to both Bcr-Abl proteins. Tyrosine 69-77 growth factor receptor bound protein 2 Homo sapiens 14-18 7506413-8 1994 On the other hand, tyrosine phosphorylation of Shc, complex formation of Shc-Grb2/Ash, and activation of microtubule-associated protein kinase were still fully induced upon EGF stimulation without binding of Shc or Grb2/Ash to the mutant receptor. Tyrosine 19-27 growth factor receptor bound protein 2 Homo sapiens 220-223 8282127-2 1993 Insulin promotes the formation of a complex between tyrosine-phosphorylated IRS-1 and several proteins including phosphoinositide(PI) 3-kinase, a heterodimer consisting of regulatory 85-kDa (p85) and catalytic 110-kDa (p110) subunits, GRB2 and Syp via the Src homology region 2 (SH2) domains. Tyrosine 52-60 growth factor receptor bound protein 2 Homo sapiens 235-239 8264620-7 1994 Using a panel of PDGF beta-receptor mutants with altered tyrosine phosphorylation sites, we identified Tyr-1009 in the PDGF receptor as required for GRB2 binding. Tyrosine 103-106 growth factor receptor bound protein 2 Homo sapiens 149-153 8264620-11 1994 Furthermore, both GRB2 and Sos coimmunoprecipitate with Syp from lysates of PDGF-stimulated cells, and GRB2 binds directly to tyrosine-phosphorylated Syp in vitro. Tyrosine 126-134 growth factor receptor bound protein 2 Homo sapiens 18-22 8264620-11 1994 Furthermore, both GRB2 and Sos coimmunoprecipitate with Syp from lysates of PDGF-stimulated cells, and GRB2 binds directly to tyrosine-phosphorylated Syp in vitro. Tyrosine 126-134 growth factor receptor bound protein 2 Homo sapiens 103-107 7504175-7 1993 By contrast, the SH2 domain in GRB2 and the amino-terminal SH2 domain in SHPTP2 (Syp) specifically bind to Tyr(P)-895 and Tyr(P)-1172, respectively. Tyrosine 107-110 growth factor receptor bound protein 2 Homo sapiens 31-35 7504175-7 1993 By contrast, the SH2 domain in GRB2 and the amino-terminal SH2 domain in SHPTP2 (Syp) specifically bind to Tyr(P)-895 and Tyr(P)-1172, respectively. Tyrosine 122-125 growth factor receptor bound protein 2 Homo sapiens 31-35 8388384-13 1993 We also demonstrated that fusion protein of ASH was able to bind the fusion protein of tyrosine-phosphorylated IRS-1 fragments, suggesting that ASH is able to bind tyrosine-phosphorylated IRS-1 directly. Tyrosine 164-172 growth factor receptor bound protein 2 Homo sapiens 144-147 8235613-1 1993 The shc oncogene product is tyrosine-phosphorylated by Src family kinases and after its phosphorylation interacts with the adapter protein Grb2 (growth factor receptor-bound protein 2). Tyrosine 28-36 growth factor receptor bound protein 2 Homo sapiens 139-143 8235613-1 1993 The shc oncogene product is tyrosine-phosphorylated by Src family kinases and after its phosphorylation interacts with the adapter protein Grb2 (growth factor receptor-bound protein 2). Tyrosine 28-36 growth factor receptor bound protein 2 Homo sapiens 145-183 8388384-8 1993 We have studied an interaction of ASH with insulin-stimulated tyrosine-phosphorylated proteins in Chinese hamster ovary cells overexpressing human insulin receptors (CHO-HIR cells). Tyrosine 62-70 growth factor receptor bound protein 2 Homo sapiens 34-37 7691810-0 1993 Multiple cytokines induce the tyrosine phosphorylation of Shc and its association with Grb2 in hemopoietic cells. Tyrosine 30-38 growth factor receptor bound protein 2 Homo sapiens 87-91 7691810-4 1993 We also show that upon tyrosine phosphorylation, p52shc becomes associated with the adaptor protein, Grb2. Tyrosine 23-31 growth factor receptor bound protein 2 Homo sapiens 101-105 8402896-5 1993 Binding of GRB-2 to BCR-ABL is mediated by the direct interaction of the GRB-2 SH2 domain with a phosphorylated tyrosine, Y177, within the BCR first exon. Tyrosine 112-120 growth factor receptor bound protein 2 Homo sapiens 11-16 8402896-5 1993 Binding of GRB-2 to BCR-ABL is mediated by the direct interaction of the GRB-2 SH2 domain with a phosphorylated tyrosine, Y177, within the BCR first exon. Tyrosine 112-120 growth factor receptor bound protein 2 Homo sapiens 73-78 8388384-12 1993 Incubation of an ASH fusion protein with the lysates of insulin-stimulated CHO-HIR cells revealed that the fusion protein of ASH was able to bind the tyrosine-phosphorylated 170-kDa protein that was recognized by alpha IRS-1. Tyrosine 150-158 growth factor receptor bound protein 2 Homo sapiens 17-20 8388384-12 1993 Incubation of an ASH fusion protein with the lysates of insulin-stimulated CHO-HIR cells revealed that the fusion protein of ASH was able to bind the tyrosine-phosphorylated 170-kDa protein that was recognized by alpha IRS-1. Tyrosine 150-158 growth factor receptor bound protein 2 Homo sapiens 125-128 8388384-13 1993 We also demonstrated that fusion protein of ASH was able to bind the fusion protein of tyrosine-phosphorylated IRS-1 fragments, suggesting that ASH is able to bind tyrosine-phosphorylated IRS-1 directly. Tyrosine 87-95 growth factor receptor bound protein 2 Homo sapiens 44-47 35451751-7 2022 Using this method, we identified and verified two proteins, growth factor receptor binding-2 (GRB2) and phosphoinositide 3"-kinase (PI3Kp85), binding to the tyrosine 1214 of VEGFR2. Tyrosine 157-165 growth factor receptor bound protein 2 Homo sapiens 60-92 8388384-13 1993 We also demonstrated that fusion protein of ASH was able to bind the fusion protein of tyrosine-phosphorylated IRS-1 fragments, suggesting that ASH is able to bind tyrosine-phosphorylated IRS-1 directly. Tyrosine 87-95 growth factor receptor bound protein 2 Homo sapiens 144-147 8388384-13 1993 We also demonstrated that fusion protein of ASH was able to bind the fusion protein of tyrosine-phosphorylated IRS-1 fragments, suggesting that ASH is able to bind tyrosine-phosphorylated IRS-1 directly. Tyrosine 164-172 growth factor receptor bound protein 2 Homo sapiens 44-47 8491186-0 1993 The SH2/SH3 domain-containing protein GRB2 interacts with tyrosine-phosphorylated IRS1 and Shc: implications for insulin control of ras signalling. Tyrosine 58-66 growth factor receptor bound protein 2 Homo sapiens 38-42 8491186-3 1993 In this report we show that in response to insulin, GRB2 forms a stable complex with two tyrosine-phosphorylated proteins. Tyrosine 89-97 growth factor receptor bound protein 2 Homo sapiens 52-56 8491186-8 1993 Interestingly, both GRB2 and phosphatidylinositol-3 (PI-3) kinase can simultaneously bind distinct tyrosine phosphorylated regions on the same IRS-1 molecule, suggesting a mechanism whereby IRS-1 could provide the core for a large signalling complex. Tyrosine 99-107 growth factor receptor bound protein 2 Homo sapiens 20-24 7521298-8 1994 Thus the binding of Grb2 to a receptor or to an associated protein phosphorylated on tyrosines is unlikely to activate the exchange factor activity of Sos through a conformational change transmitted from the SH2 to the SH3 domains. Tyrosine 85-94 growth factor receptor bound protein 2 Homo sapiens 20-24 1465135-5 1992 Here we report that tyrosine-phosphorylated Shc proteins form a specific complex with a non-phosphorylated 23K polypeptide encoded by the grb2/sem-5 gene. Tyrosine 20-28 growth factor receptor bound protein 2 Homo sapiens 138-142 1465135-8 1992 These results suggest that Shc tyrosine phosphorylation can couple tyrosine kinases to Grb2/Sem-5, through formation of a Shc-Grb2/Sem-5 complex, and thereby regulate the mammalian Ras signalling pathway. Tyrosine 31-39 growth factor receptor bound protein 2 Homo sapiens 87-91 1465135-8 1992 These results suggest that Shc tyrosine phosphorylation can couple tyrosine kinases to Grb2/Sem-5, through formation of a Shc-Grb2/Sem-5 complex, and thereby regulate the mammalian Ras signalling pathway. Tyrosine 31-39 growth factor receptor bound protein 2 Homo sapiens 126-130 35451751-7 2022 Using this method, we identified and verified two proteins, growth factor receptor binding-2 (GRB2) and phosphoinositide 3"-kinase (PI3Kp85), binding to the tyrosine 1214 of VEGFR2. Tyrosine 157-165 growth factor receptor bound protein 2 Homo sapiens 94-98