Grb2

Summary

Gene Symbol: Grb2
Description: growth factor receptor bound protein 2
Alias: AA408164, Ash, growth factor receptor-bound protein 2, SH2/SH3 adapter GRB2, adapter protein GRB2
Species: mouse
Products:     Grb2

Top Publications

  1. Gong Q, Cheng A, Akk A, Alberola Ila J, Gong G, Pawson T, et al. Disruption of T cell signaling networks and development by Grb2 haploid insufficiency. Nat Immunol. 2001;2:29-36 pubmed
    ..We show here that decreased expression of the adaptor protein Grb2 in Grb2+/- mice weakens TCR-induced c-Jun N-terminal kinase (JNK) and p38, but not extracellular signal-regulated ..
  2. Zhou D, Noviello C, D Ambrosio C, Scaloni A, D ADAMIO L. 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. J Biol Chem. 2004;279:25374-80 pubmed
    ..Here we describe a protein, growth factor receptor-bound protein 2 (Grb2), that specifically binds AbetaPP, phosphorylated in Tyr(682)...
  3. Johnson A, Aravind L, Shulzhenko N, Morgun A, Choi S, Crockford T, et al. Themis is a member of a new metazoan gene family and is required for the completion of thymocyte positive selection. Nat Immunol. 2009;10:831-9 pubmed publisher
    ..Our data suggest a unique function for Themis in sustaining positive selection. ..
  4. Goyal R, Lin P, Kanungo J, Payne A, Muslin A, Longmore G. Ajuba, a novel LIM protein, interacts with Grb2, augments mitogen-activated protein kinase activity in fibroblasts, and promotes meiotic maturation of Xenopus oocytes in a Grb2- and Ras-dependent manner. Mol Cell Biol. 1999;19:4379-89 pubmed
    ..The pre-LIM domain contains two putative proline-rich SH3 recognition motifs. Ajuba specifically associated with Grb2 in vitro and in vivo...
  5. Schlaepfer D, Jones K, Hunter T. 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. Mol Cell Biol. 1998;18:2571-85 pubmed
    ..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...
  6. Lowenstein E, Daly R, Batzer A, Li W, Margolis B, Lammers R, et al. The SH2 and SH3 domain-containing protein GRB2 links receptor tyrosine kinases to ras signaling. Cell. 1992;70:431-42 pubmed
    A cDNA clone encoding a novel, widely expressed protein (called growth factor receptor-bound protein 2 or GRB2) containing one src homology 2 (SH2) domain and two SH3 domains was isolated...
  7. Findlay G, Smith M, Lanner F, Hsiung M, Gish G, Petsalaki E, et al. Interaction domains of Sos1/Grb2 are finely tuned for cooperative control of embryonic stem cell fate. Cell. 2013;152:1008-20 pubmed publisher
    ..The Ras guanine nucleotide exchange factor (RasGEF) Sos1 and its adaptor Grb2 are multidomain proteins that couple fibroblast growth factor (FGF) signaling to activation of the Ras-Erk pathway ..
  8. Cheng S, Sun G, Schlaepfer D, Pallen C. Grb2 promotes integrin-induced focal adhesion kinase (FAK) autophosphorylation and directs the phosphorylation of protein tyrosine phosphatase ? by the Src-FAK kinase complex. Mol Cell Biol. 2014;34:348-61 pubmed publisher
    ..The adaptor protein Grb2 is also recruited by PTP?-phospho-Tyr789, although the role of the PTP?-Grb2 complex in integrin signaling is ..
  9. Lesourne R, Uehara S, Lee J, Song K, Li L, Pinkhasov J, et al. Themis, a T cell-specific protein important for late thymocyte development. Nat Immunol. 2009;10:840-7 pubmed publisher
    ..Our results identify Themis as a critical component of the T cell developmental program and suggest that Themis functions to sustain and/or integrate signals required for proper lineage commitment and maturation. ..

More Information

Publications92

  1. Kouhara H, Hadari Y, Spivak Kroizman T, Schilling J, Bar Sagi D, Lax I, et al. A lipid-anchored Grb2-binding protein that links FGF-receptor activation to the Ras/MAPK signaling pathway. Cell. 1997;89:693-702 pubmed
    ..cloning, and characterization of a novel protein, designated FRS2, that is tyrosine phosphorylated and binds to Grb2/Sos in response to FGF or NGF stimulation...
  2. Gout I, Dhand R, Hiles I, Fry M, Panayotou G, Das P, et al. The GTPase dynamin binds to and is activated by a subset of SH3 domains. Cell. 1993;75:25-36 pubmed
    ..occurs through proline-rich sequence motifs similar to those that mediate the interaction of the SH3 domains of Grb2 and Abl proteins to the guanine nucleotide exchange protein, Sos, and to the 3BP1 protein, respectively...
  3. Maina F, Casagranda F, Audero E, Simeone A, Comoglio P, Klein R, et al. Uncoupling of Grb2 from the Met receptor in vivo reveals complex roles in muscle development. Cell. 1996;87:531-42 pubmed
    ..In contrast, disrupting the consensus for Grb2 binding allowed development to proceed to term without affecting placenta and liver but caused a striking reduction ..
  4. Rozakis Adcock M, McGlade J, Mbamalu G, Pelicci G, Daly R, Li W, et al. Association of the Shc and Grb2/Sem5 SH2-containing proteins is implicated in activation of the Ras pathway by tyrosine kinases. Nature. 1992;360:689-92 pubmed
    ..Shc proteins form a specific complex with a non-phosphorylated 23K polypeptide encoded by the grb2/sem-5 gene...
  5. Patrick M, Oda H, Hayakawa K, Sato Y, Eshima K, Kirikae T, et al. Gasp, a Grb2-associating protein, is critical for positive selection of thymocytes. Proc Natl Acad Sci U S A. 2009;106:16345-50 pubmed publisher
    ..Here, we identified and characterized a gene product Gasp (Grb2-associating protein, also called Themis) that is critically required for positive selection...
  6. Suen K, Bustelo X, Pawson T, Barbacid M. Molecular cloning of the mouse grb2 gene: differential interaction of the Grb2 adaptor protein with epidermal growth factor and nerve growth factor receptors. Mol Cell Biol. 1993;13:5500-12 pubmed
    We report the isolation and molecular characterization of the mouse grb2 gene...
  7. Seykora J, Mei L, Dotto G, Stein P. 'Srcasm: a novel Src activating and signaling molecule. J Biol Chem. 2002;277:2812-22 pubmed
    ..Srcasm is capable of interacting with Grb2 and the regulatory subunit of phosphoinositide 3-kinase, p85, in a phosphorylation-dependent manner...
  8. Rozakis Adcock M, Fernley R, Wade J, Pawson T, Bowtell D. The SH2 and SH3 domains of mammalian Grb2 couple the EGF receptor to the Ras activator mSos1. Nature. 1993;363:83-5 pubmed
    ..Sem-5 is homologous to the mammalian protein Grb2, which binds the autophosphorylated EGF receptor and other phosphotyrosine-containing proteins such as Shc through ..
  9. Cheng A, Saxton T, Sakai R, Kulkarni S, Mbamalu G, Vogel W, et al. Mammalian Grb2 regulates multiple steps in embryonic development and malignant transformation. Cell. 1998;95:793-803 pubmed
    ..the biological functions of a mammalian SH2/SH3 adaptor, we have introduced a null mutation into the mouse gene for Grb2. Analysis of mutant embryonic stem cells, embryos, and chimeras reveals that Grb2 is required during embyrogenesis ..
  10. Garg P, Verma R, Nihalani D, Johnstone D, Holzman L. Neph1 cooperates with nephrin to transduce a signal that induces actin polymerization. Mol Cell Biol. 2007;27:8698-712 pubmed
    ..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...
  11. Schaeper U, Gehring N, Fuchs K, Sachs M, Kempkes B, Birchmeier W. Coupling of Gab1 to c-Met, Grb2, and Shp2 mediates biological responses. J Cell Biol. 2000;149:1419-32 pubmed
    ..In addition, Gab1 is engaged in a constitutive complex with the adaptor protein Grb2. We have now mapped the c-Met and Grb2 interaction sites using reverse yeast two-hybrid technology...
  12. Koonpaew S, Janssen E, Zhu M, Zhang W. The importance of three membrane-distal tyrosines in the adaptor protein NTAL/LAB. J Biol Chem. 2004;279:11229-35 pubmed
    ..Upon engagement of the B cell receptor or Fc receptors, it is phosphorylated and interacts with Grb2. LAB is capable of rescuing thymocyte development in LAT(-/-) mice...
  13. den Hertog J, Tracy S, Hunter T. Phosphorylation of receptor protein-tyrosine phosphatase alpha on Tyr789, a binding site for the SH3-SH2-SH3 adaptor protein GRB-2 in vivo. EMBO J. 1994;13:3020-32 pubmed
    ..on the C-terminal side of Tyr789 (YANF) fits the consensus binding site for the SH3-SH2-SH3 adaptor protein GRB2 (YXNX)...
  14. Wright J, Reuter C, Weber M. An incomplete program of cellular tyrosine phosphorylations induced by kinase-defective epidermal growth factor receptors. J Biol Chem. 1995;270:12085-93 pubmed
    ..Thus, heterodimerization with and activation of endogenous ErbB2/c-Neu is a possible mechanism by which kinase-defective receptors stimulate the MAP kinase pathway. ..
  15. Wolf I, Jenkins B, Liu Y, Seiffert M, Custodio J, Young P, et al. Gab3, a new DOS/Gab family member, facilitates macrophage differentiation. Mol Cell Biol. 2002;22:231-44 pubmed
    ..These results suggest that Gab3 is important for macrophage differentiation and that differentiation requires the early phosphorylation of Gab2 followed by induction and subsequent phosphorylation of Gab3. ..
  16. Jiang S, Chiou Y, Wang E, Lin H, Lin Y, Chi Y, et al. Defining a link with autosomal-dominant polycystic kidney disease in mice with congenitally low expression of Pkd1. Am J Pathol. 2006;168:205-20 pubmed
    ..Abnormalities in Na(+)/K(+)-ATPase, aquaporin-2, and vasopressin V2 receptor expression were also identified. This mouse model may be suitable for further studies of progression and therapeutic interventions of ADPKD. ..
  17. Peng Y, Lu Z, Li G, Piechowicz M, Anderson M, Uddin Y, et al. The autism-associated MET receptor tyrosine kinase engages early neuronal growth mechanism and controls glutamatergic circuits development in the forebrain. Mol Psychiatry. 2016;21:925-35 pubmed publisher
    ..Dysregulated MET signaling may lead to pathological changes in forebrain maturation and connectivity, and thus contribute to the emergence of neurological symptoms associated with ASD. ..
  18. Lee M, Pardoux C, Hall M, Lee P, Warburton D, Qing J, et al. TGF-beta activates Erk MAP kinase signalling through direct phosphorylation of ShcA. EMBO J. 2007;26:3957-67 pubmed
    ..TGF-beta-induced ShcA phosphorylation induces ShcA association with Grb2 and Sos, thereby initiating the well-characterised pathway linking receptor tyrosine kinases with Erk MAP kinases...
  19. Liu X, Liu M, Zhang J, Bai X, Ramos F, Van Remmen H, et al. Downregulation of Grb2 contributes to the insulin-sensitizing effect of calorie restriction. Am J Physiol Endocrinol Metab. 2009;296:E1067-75 pubmed publisher
    ..found that CR of mice (60% of the diet consumption compared with ad libitum mice) reduces the expression levels of Grb2 in skeletal muscle, an insulin target tissue that accounts for 85% of insulin-stimulated blood glucose clearance...
  20. Salvatore P, Hanash C, Kido Y, Imai Y, Accili D. Identification of sirm, a novel insulin-regulated SH3 binding protein that associates with Grb-2 and FYN. J Biol Chem. 1998;273:6989-97 pubmed
    ..Based on the patterns of expression of sirm, its regulation by insulin, and the interactions with molecules in the insulin signaling pathway, we surmise that Sirm plays a role in modulating tissue sensitivity to insulin. ..
  21. Lysek D, Wuthrich K. Prion protein interaction with the C-terminal SH3 domain of Grb2 studied using NMR and optical spectroscopy. Biochemistry. 2004;43:10393-9 pubmed
    ..paper investigated the binding of the C-terminal SH3 domain of the murine growth factor receptor-bound protein 2 (Grb2) to the murine PrP, using NMR, fluorescence, and circular dichroism spectroscopy...
  22. Kanagasundaram V, Jaworowski A, Byrne R, Hamilton J. Separation and characterization of the activated pool of colony-stimulating factor 1 receptor forming distinct multimeric complexes with signalling molecules in macrophages. Mol Cell Biol. 1999;19:4079-92 pubmed
    ..A small pool of CSF-1R formed a multimeric complex with phosphatidylinositol-3 kinase (PI-3 kinase), SHP-1, Grb2, Shc, c-Src, Cbl, and a significant number of tyrosine-phosphorylated proteins in CSF-1-stimulated cells...
  23. Jones N, Master Z, Jones J, Bouchard D, Gunji Y, Sasaki H, et al. Identification of Tek/Tie2 binding partners. Binding to a multifunctional docking site mediates cell survival and migration. J Biol Chem. 1999;274:30896-905 pubmed
    ..Using this approach, we demonstrate that five molecules, Grb2, Grb7, Grb14, Shp2, and the p85 subunit of phosphatidylinositol 3-kinase can interact with Tek in a phosphotyrosine-..
  24. Li N, Lorinczi M, Ireton K, Elferink L. Specific Grb2-mediated interactions regulate clathrin-dependent endocytosis of the cMet-tyrosine kinase. J Biol Chem. 2007;282:16764-75 pubmed
    ..Cbl can directly bind cMet at phosphotyrosine 1003 or indirectly via Grb2 to phosphotyrosine 1356 in the multisubstrate binding domain of cMet...
  25. Baksi S, Jana N, Bhattacharyya N, Mukhopadhyay D. Grb2 is regulated by foxd3 and has roles in preventing accumulation and aggregation of mutant huntingtin. PLoS ONE. 2013;8:e76792 pubmed publisher
    Growth factor receptor protein binding protein 2 (Grb2) is known to be associated with intracellular growth and proliferation related signaling cascades...
  26. Gross I, Bassit B, Benezra M, Licht J. Mammalian sprouty proteins inhibit cell growth and differentiation by preventing ras activation. J Biol Chem. 2001;276:46460-8 pubmed
    ..We further showed that Sprouty1 and Sprouty2 do no prevent the formation of a SNT.Grb2.Sos complex upon fibroblast growth factor stimulation, yet block Ras activation...
  27. Zhang S, Weinheimer C, Courtois M, Kovacs A, Zhang C, Cheng A, et al. The role of the Grb2-p38 MAPK signaling pathway in cardiac hypertrophy and fibrosis. J Clin Invest. 2003;111:833-41 pubmed
    ..heart can result in the integrin-mediated activation of focal adhesion kinase and the subsequent recruitment of the Grb2 adapter molecule...
  28. Peirce M, Brook M, Morrice N, Snelgrove R, Begum S, Lanfrancotti A, et al. Themis2/ICB1 is a signaling scaffold that selectively regulates macrophage Toll-like receptor signaling and cytokine production. PLoS ONE. 2010;5:e11465 pubmed publisher
    ..with Lyn kinase (P25911), the Rho guanine nucleotide exchange factor, Vav (P27870), and the adaptor protein Grb2 (Q60631)...
  29. Wittekind M, Mapelli C, Lee V, Goldfarb V, Friedrichs M, Meyers C, et al. Solution structure of the Grb2 N-terminal SH3 domain complexed with a ten-residue peptide derived from SOS: direct refinement against NOEs, J-couplings and 1H and 13C chemical shifts. J Mol Biol. 1997;267:933-52 pubmed
    Refined ensembles of solution structures have been calculated for the N-terminal SH3 domain of Grb2 (N-SH3) complexed with the ac-VPPPVPPRRR-nh2 peptide derived from residues 1135 to 1144 of the mouse SOS-1 sequence...
  30. Odai H, Sasaki K, Hanazono Y, Ueno H, Tanaka T, Miyagawa K, et al. c-Cbl is inducibly tyrosine-phosphorylated by epidermal growth factor stimulation in fibroblasts, and constitutively tyrosine-phosphorylated and associated with v-Src in v-src-transformed fibroblasts. Jpn J Cancer Res. 1995;86:1119-26 pubmed
    ..These findings strongly suggest that c-Cbl is implicated in a wide variety of signal transduction pathways, including those of EGF receptor and Src protein, as well as in the signaling pathways of hematopoietic cells. ..
  31. Rozakis Adcock M, van der Geer P, Mbamalu G, Pawson T. MAP kinase phosphorylation of mSos1 promotes dissociation of mSos1-Shc and mSos1-EGF receptor complexes. Oncogene. 1995;11:1417-26 pubmed
    ..C-terminal tail which contains several potential binding sites for the SH3 domains of the adaptor protein, Grb2. In fibroblasts, growth factor stimulation results in the recruitment of Grb2-mSos1 into complexes with activated ..
  32. Zhang S, Ren J, Khan M, Cheng A, Abendschein D, Muslin A. Grb2 is required for the development of neointima in response to vascular injury. Arterioscler Thromb Vasc Biol. 2003;23:1788-93 pubmed
    ..In this work, the role of the intracellular linker protein Grb2 in the pathogenesis of neointima formation was examined...
  33. Yokoyama N, Malbon C. Dishevelled-2 docks and activates Src in a Wnt-dependent manner. J Cell Sci. 2009;122:4439-51 pubmed publisher
    ..Activated Src, in turn, enhances Wnt activation of the canonical pathway. We show that Dvl2 and beta-catenin are crucially important substrates for tyrosine phosphorylation in the canonical Wnt/beta-catenin pathway. ..
  34. Watanabe K, Ma M, Hirabayashi K, Gurusamy N, Veeraveedu P, Prakash P, et al. Swimming stress in DN 14-3-3 mice triggers maladaptive cardiac remodeling: role of p38 MAPK. Am J Physiol Heart Circ Physiol. 2007;292:H1269-77 pubmed
    ..These results indicate for the first time that 14-3-3 protein along with p38 MAPK plays a crucial role in left ventricular remodeling associated with swimming stress. ..
  35. Thornhill P, Cohn J, Stanford W, Desbarats J. The adaptor protein Grb2 regulates cell surface Fas ligand in Schwann cells. Biochem Biophys Res Commun. 2008;376:341-6 pubmed publisher
    ..Here, we show that Grb2, an SH3 domain-containing adaptor protein, binds to the proline-rich domain of FasL and regulates its cell surface ..
  36. Borinstein S, Hyatt M, Sykes V, Straub R, Lipkowitz S, Boulter J, et al. SETA is a multifunctional adapter protein with three SH3 domains that binds Grb2, Cbl, and the novel SB1 proteins. Cell Signal. 2000;12:769-79 pubmed
    ..Evidence that SETA binds to the CD2 protein, the proto-oncogene c-Cbl, and the signal transduction molecule Grb2, and can dimerize via its C-terminal coiled coil (CC) domain is also presented.
  37. Taylor S, Anafi M, Pawson T, Shalloway D. Functional interaction between c-Src and its mitotic target, Sam 68. J Biol Chem. 1995;270:10120-4 pubmed
    ..different affinities (c-Src approximately Ras GTPase activating protein > p85 alpha (amino-terminal) > Grb2 > p85 alpha (COOH-terminal))...
  38. Ravichandran K, Lorenz U, Shoelson S, Burakoff S. Interaction of Shc with Grb2 regulates association of Grb2 with mSOS. Mol Cell Biol. 1995;15:593-600 pubmed
    ..the simultaneous interaction of phosphorylated Shc with the TCR zeta chain and with a second adapter protein, Grb2. Grb2, in turn, interacts with the Ras guanine nucleotide exchange factor mSOS, thereby leading to Ras activation...
  39. Johnson K, Lane P, Cook S, Harris B, Ward Bailey P, Bronson R, et al. Curly bare (cub), a new mouse mutation on chromosome 11 causing skin and hair abnormalities, and a modifier gene (mcub) on chromosome 5. Genomics. 2003;81:6-14 pubmed
    ..The similarity of the wavy coat phenotype to those of Tgfa and Egfr mutations and the map positions of cub and mcub suggest candidate genes that interact in the EGF receptor signal transduction pathway. ..
  40. Yamaguchi A, Urano T, Goi T, Feig L. An Eps homology (EH) domain protein that binds to the Ral-GTPase target, RalBP1. J Biol Chem. 1997;272:31230-4 pubmed
    ..In addition, Reps1 has the capacity to form a complex with the SH3 domains of the adapter proteins Crk and Grb2, which may link Reps1 to an EGF-responsive tyrosine kinase...
  41. Jamora C, Lee P, Kocieniewski P, Azhar M, Hosokawa R, Chai Y, et al. A signaling pathway involving TGF-beta2 and snail in hair follicle morphogenesis. PLoS Biol. 2005;3:e11 pubmed
    ..This novel signaling pathway further weaves together the web of different morphogens and downstream transcriptional events that guide hair bud formation within the developing skin. ..
  42. Ursini Siegel J, Hardy W, Zuo D, Lam S, Sanguin Gendreau V, Cardiff R, et al. ShcA signalling is essential for tumour progression in mouse models of human breast cancer. EMBO J. 2008;27:910-20 pubmed publisher
    ..This study is the first to directly demonstrate that signalling downstream from the ShcA adaptor protein is critical for breast cancer development. ..
  43. Garzotto D, Giacobini P, Crepaldi T, Fasolo A, De Marchis S. Hepatocyte growth factor regulates migration of olfactory interneuron precursors in the rostral migratory stream through Met-Grb2 coupling. J Neurosci. 2008;28:5901-9 pubmed publisher
    ..with a point mutation in the Met receptor that impairs signal transduction through the Ras/MAP kinase pathway (Met(Grb2/Grb2)) shows that without Met-Grb2 binding, neuroblast migration is reduced...
  44. Mitra P, Thanabalu T. Myogenic differentiation depends on the interplay of Grb2 and N-WASP. Biochim Biophys Acta Mol Cell Res. 2017;1864:487-497 pubmed publisher
    ..b>Grb2 is an adaptor protein whose central SH2 domain binds to phosphorylated tyrosine residues of activated receptors and ..
  45. Jain S, Langdon W, Varticovski L. Tyrosine phosphorylation of p120cbl in BCR/abl transformed hematopoietic cells mediates enhanced association with phosphatidylinositol 3-kinase. Oncogene. 1997;14:2217-28 pubmed
    ..Our experiments show that, in contrast to other cell types, the in vivo interaction of cbl with GRB2 and p85 is significantly enhanced in BCR/abl transformed BaF3 cells and that tyrosine phosphorylation of cbl leads ..
  46. Giannoni E, Raugei G, Chiarugi P, Ramponi G. A novel redox-based switch: LMW-PTP oxidation enhances Grb2 binding and leads to ERK activation. Biochem Biophys Res Commun. 2006;348:367-73 pubmed
    ..we observed a selective hyper-phosphorylation of Tyr132, that acts as a docking site for the adaptor protein Grb2. The redox-dependent enhancement of Grb2 recruitment to LMW-PTP ultimately leads to an improvement of ERK ..
  47. Grandal M, Zandi R, Pedersen M, Willumsen B, van Deurs B, Poulsen H. EGFRvIII escapes down-regulation due to impaired internalization and sorting to lysosomes. Carcinogenesis. 2007;28:1408-17 pubmed
    ..EGFRvIII binds the ubiquitin ligase c-Cbl via Grb2, whereas binding via phosphorylated tyrosine residue 1045 seems to be limited...
  48. Vindis C, Cerretti D, Daniel T, Huynh Do U. EphB1 recruits c-Src and p52Shc to activate MAPK/ERK and promote chemotaxis. J Cell Biol. 2003;162:661-71 pubmed
    ..Here we demonstrate that activated EphB1 recruits the adaptor proteins Grb2 and p52Shc and promotes p52Shc and c-Src tyrosine phosphorylation as well as MAPK/extracellular signal-regulated ..
  49. Weinger J, Gohari P, Yan Y, Backer J, Varnum B, Shafit Zagardo B. In brain, Axl recruits Grb2 and the p85 regulatory subunit of PI3 kinase; in vitro mutagenesis defines the requisite binding sites for downstream Akt activation. J Neurochem. 2008;106:134-46 pubmed publisher
    ..and mutant Axl transfected cells determined that Axl directly binds growth factor receptor-bound protein 2 (Grb2) at pYVN and the p85 subunit of phosphatidylinositol-3 kinase (PI3 kinase) at two pYXXM sites (pY779 and pY821)...
  50. Ogura K, Nagata K, Horiuchi M, Ebisui E, Hasuda T, Yuzawa S, et al. Solution structure of N-terminal SH3 domain of Vav and the recognition site for Grb2 C-terminal SH3 domain. J Biomol NMR. 2002;22:37-46 pubmed
    ..The C-terminal SH3 domain of Grb2 specifically binds to the trans form of the N-terminal SH3 domain of Vav...
  51. Ren R, Mayer B, Cicchetti P, Baltimore D. Identification of a ten-amino acid proline-rich SH3 binding site. Science. 1993;259:1157-61 pubmed
    ..Identification of the SH3 binding site provides a basis for understanding the interaction between the SH3 domains and their targets. ..
  52. Dráber P, Vonkova I, Stepanek O, Hrdinka M, Kucova M, Skopcova T, et al. SCIMP, a transmembrane adaptor protein involved in major histocompatibility complex class II signaling. Mol Cell Biol. 2011;31:4550-62 pubmed publisher
    ..The results suggest that SCIMP is involved in signal transduction after MHC-II stimulation and therefore serves as a regulator of antigen presentation and other APC functions. ..
  53. Stork B, Engelke M, Frey J, Horejsi V, Hamm Baarke A, Schraven B, et al. Grb2 and the non-T cell activation linker NTAL constitute a Ca(2+)-regulating signal circuit in B lymphocytes. Immunity. 2004;21:681-91 pubmed
    ..Phosphorylated NTAL recruits the Grb2 linker, but downstream signaling cascades are unclear...
  54. Kato M, Miyazawa K, Kitamura N. A deubiquitinating enzyme UBPY interacts with the Src homology 3 domain of Hrs-binding protein via a novel binding motif PX(V/I)(D/N)RXXKP. J Biol Chem. 2000;275:37481-7 pubmed
    ..Ubiquitination of growth factor receptors is thought to regulate their intracellular degradation. Thus, UBPY may play a regulatory role in the degradation by interaction with the SH3 domain of Hbp via the novel SH3-binding motif. ..
  55. Ishii H, Inageta T, Mimori K, Saito T, Sasaki H, Isobe M, et al. Frag1, a homolog of alternative replication factor C subunits, links replication stress surveillance with apoptosis. Proc Natl Acad Sci U S A. 2005;102:9655-60 pubmed
  56. Saxton T, Cheng A, Ong S, Lu Y, Sakai R, Cross J, et al. Gene dosage-dependent functions for phosphotyrosine-Grb2 signaling during mammalian tissue morphogenesis. Curr Biol. 2001;11:662-70 pubmed
    The mammalian Grb2 adaptor protein binds pTyr-X-Asn motifs through its SH2 domain, and engages downstream targets such as Sos1 and Gab1 through its SH3 domains...
  57. Lu W, Gong D, Bar Sagi D, Cole P. Site-specific incorporation of a phosphotyrosine mimetic reveals a role for tyrosine phosphorylation of SHP-2 in cell signaling. Mol Cell. 2001;8:759-69 pubmed
    ..These studies support a novel mechanism explaining how tyrosine phosphorylation of a PTPase is important in signal transduction. ..
  58. Hartman Z, Zhao H, Agazie Y. HER2 stabilizes EGFR and itself by altering autophosphorylation patterns in a manner that overcomes regulatory mechanisms and promotes proliferative and transformation signaling. Oncogene. 2013;32:4169-80 pubmed publisher
    ..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 ..
  59. Williams L, Kalantry S, Starmer J, Magnuson T. Transcription precedes loss of Xist coating and depletion of H3K27me3 during X-chromosome reprogramming in the mouse inner cell mass. Development. 2011;138:2049-57 pubmed publisher
  60. Salojin K, Zhang J, Cameron M, Gill B, Arreaza G, Ochi A, et al. Impaired plasma membrane targeting of Grb2-murine son of sevenless (mSOS) complex and differential activation of the Fyn-T cell receptor (TCR)-zeta-Cbl pathway mediate T cell hyporesponsiveness in autoimmune nonobese diabetic mice. J Exp Med. 1997;186:887-97 pubmed
    ..from the cytoplasm to the plasma membrane; and (c) exclusion of mSOS and PLC-gamma1 from the TCR-zeta-associated Grb2/pp36-38/ZAP70 signaling complex...
  61. Gingras J, Gawor M, Bernadzki K, Grady R, Hallock P, Glass D, et al. Α-Dystrobrevin-1 recruits Grb2 and α-catulin to organize neurotransmitter receptors at the neuromuscular junction. J Cell Sci. 2016;129:898-911 pubmed publisher
    ..They include multiple members of the DGC, as well as α-catulin, liprin-α1, Usp9x, PI3K, Arhgef5 and Grb2. Finally, we show that two interactors, α-catulin (phosphorylation independent) and Grb2 (phosphorylation ..
  62. Higuchi T, Orita T, Katsuya K, Yamasaki Y, Akiyama K, Li H, et al. MUC20 suppresses the hepatocyte growth factor-induced Grb2-Ras pathway by binding to a multifunctional docking site of met. Mol Cell Biol. 2004;24:7456-68 pubmed
    ..C terminus of MUC20 associates with the multifunctional docking site of Met without ligand activation, preventing Grb2 recruitment to Met and thus attenuating hepatocyte growth factor (HGF)-induced transient extracellular signal-..
  63. Zhu M, Liu Y, Koonpaew S, Granillo O, Zhang W. Positive and negative regulation of FcepsilonRI-mediated signaling by the adaptor protein LAB/NTAL. J Exp Med. 2004;200:991-1000 pubmed
    ..Upon BCR activation, LAB is phosphorylated and interacts with Grb2. LAB is capable of rescuing thymocyte development in LAT-deficient mice...
  64. Engels N, König L, Heemann C, Lutz J, Tsubata T, Griep S, et al. Recruitment of the cytoplasmic adaptor Grb2 to surface IgG and IgE provides antigen receptor-intrinsic costimulation to class-switched B cells. Nat Immunol. 2009;10:1018-25 pubmed publisher
    ..When phosphorylated, this tyrosine recruited the adaptor Grb2, resulting in sustained protein kinase activation and prolonged generation of second messengers, which together ..
  65. Zvezdova E, Mikolajczak J, Garreau A, Marcellin M, Rigal L, Lee J, et al. Themis1 enhances T cell receptor signaling during thymocyte development by promoting Vav1 activity and Grb2 stability. Sci Signal. 2016;9:ra51 pubmed publisher
    ..Proteomic analysis of the Themis1 interactome identified SHP-1, the TCR-associated adaptor protein Grb2, and the guanine nucleotide exchange factor Vav1 as the principal interacting partners of Themis1 in isolated mouse ..
  66. Hauck C, Hunter T, Schlaepfer D. The v-Src SH3 domain facilitates a cell adhesion-independent association with focal adhesion kinase. J Biol Chem. 2001;276:17653-62 pubmed publisher
    ..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...
  67. Galliher Beckley A, Schiemann W. Grb2 binding to Tyr284 in TbetaR-II is essential for mammary tumor growth and metastasis stimulated by TGF-beta. Carcinogenesis. 2008;29:244-51 pubmed publisher
    We demonstrated previously that growth factor receptor-bound protein 2 (Grb2) associates with the transforming growth factor-beta (TGF-beta) type II receptor [TbetaR-II] upon its phosphorylation on Tyr284 by Src...
  68. Kaneko T, Kumasaka T, Ganbe T, Sato T, Miyazawa K, Kitamura N, et al. Structural insight into modest binding of a non-PXXP ligand to the signal transducing adaptor molecule-2 Src homology 3 domain. J Biol Chem. 2003;278:48162-8 pubmed
    ..Instead, the structure of STAM2 SH3 is analogous to that of Grb2 SH3 which, in addition to normal PXXP ligands, has also been shown to moderately recognize the novel motif ..
  69. Ackermann J, Radtke D, Maurberger A, Winkler T, Nitschke L. Grb2 regulates B-cell maturation, B-cell memory responses and inhibits B-cell Ca2+ signalling. EMBO J. 2011;30:1621-33 pubmed publisher
    b>Grb2 is a ubiquitously expressed adaptor protein, which activates Ras and MAP kinases in growth factor receptor signalling, while in B-cell receptor (BCR) signalling this role is controversial...
  70. Kantonen S, Hatton N, Mahankali M, Henkels K, Park H, Cox D, et al. A novel phospholipase D2-Grb2-WASp heterotrimer regulates leukocyte phagocytosis in a two-step mechanism. Mol Cell Biol. 2011;31:4524-37 pubmed publisher
    ..We now show for the first time that phospholipase D2 (PLD2) binds to growth factor receptor-bound protein 2 (Grb2) and to the Wiskott-Aldrich syndrome protein (WASp) to form a heterotrimer complex, PLD2-Grb2-WASp, and present the ..
  71. Ahmed Z, George R, Lin C, Suen K, Levitt J, Suhling K, et al. Direct binding of Grb2 SH3 domain to FGFR2 regulates SHP2 function. Cell Signal. 2010;22:23-33 pubmed publisher
    The adaptor protein Grb2 is recruited to intracellular early signalling complexes of many receptor tyrosine kinases and plays an important role transducing signals leading to MAP kinase activation...
  72. Galisteo M, Dikic I, Batzer A, Langdon W, Schlessinger J. Tyrosine phosphorylation of the c-cbl proto-oncogene protein product and association with epidermal growth factor (EGF) receptor upon EGF stimulation. J Biol Chem. 1995;270:20242-5 pubmed
    ..elegans EGF receptor homologue. Our results indicate that p120cbl is involved in an early step in the EGF signaling pathway that is conserved from nematodes to mammals. ..
  73. Chen Z, Kolokoltsov A, Wang J, Adhikary S, Lorinczi M, Elferink L, et al. GRB2 interaction with the ecotropic murine leukemia virus receptor, mCAT-1, controls virus entry and is stimulated by virus binding. J Virol. 2012;86:1421-32 pubmed publisher
    ..Growth factor receptor-bound protein 2 (GRB2) is an adaptor protein that has been shown to couple cell surface receptors, such as epidermal growth factor ..
  74. Schnyder T, Castello A, Feest C, Harwood N, Oellerich T, Urlaub H, et al. B cell receptor-mediated antigen gathering requires ubiquitin ligase Cbl and adaptors Grb2 and Dok-3 to recruit dynein to the signaling microcluster. Immunity. 2011;34:905-18 pubmed publisher
    ..a combination of high-resolution imaging, genetics and quantitative mass spectrometry, we demonstrate that adaptors Grb2 and Dok-3, and ubiquitin ligase Cbl in signaling BCR microclusters mediate association with the microtubule motor ..
  75. Lim J, Kim H, Jeun S, Kang S, Lee K. Merlin inhibits growth hormone-regulated Raf-ERKs pathways by binding to Grb2 protein. Biochem Biophys Res Commun. 2006;340:1151-7 pubmed
    ..Moreover, it was shown that merlin interacted with endogenous growth factor receptor bound 2 (Grb2) protein and inhibited its expression...
  76. Wang D, Zheng M, Lei L, Ji J, Yao Y, Qiu Y, et al. Tespa1 is involved in late thymocyte development through the regulation of TCR-mediated signaling. Nat Immunol. 2012;13:560-8 pubmed publisher
    ..Tespa1 associated with the TCR signaling components PLC-?1 and Grb2, and Tespa1 deficiency resulted in attenuated TCR signaling, as reflected by defective activation of the Erk-AP-1 ..
  77. Yohannan J, Wienands J, Coggeshall K, Justement L. Analysis of tyrosine phosphorylation-dependent interactions between stimulatory effector proteins and the B cell co-receptor CD22. J Biol Chem. 1999;274:18769-76 pubmed
    ..recruitment of the stimulatory effector proteins phospholipase Cgamma (PLCgamma), phosphoinositide 3-kinase (PI3K), Grb2, and Syk...
  78. Yulug I, Egan S, See C, Fisher E. Mapping GRB2, a signal transduction gene in the human and the mouse. Genomics. 1994;22:313-8 pubmed
    We have mapped GRB2, a signal transduction gene whose protein product is an essential component of the pathway between tyrosine kinases (such as the epidermal growth factor receptor) and downstream proteins (such as Ras and Sos)...
  79. Otipoby K, Draves K, Clark E. CD22 regulates B cell receptor-mediated signals via two domains that independently recruit Grb2 and SHP-1. J Biol Chem. 2001;276:44315-22 pubmed
    ..Furthermore, Grb2 is inducibly recruited to CD22 in human and murine B cells...
  80. Kawada K, Upadhyay G, Ferandon S, Janarthanan S, Hall M, Vilardaga J, et al. Cell migration is regulated by platelet-derived growth factor receptor endocytosis. Mol Cell Biol. 2009;29:4508-18 pubmed publisher
    ..We showed by a series of biochemical and microscopy techniques that Grb2 serves as an adaptor protein in the formation of a ternary complex between the PDGF receptor, DOCK4, and Dynamin, ..
  81. Yasui N, Findlay G, Gish G, Hsiung M, Huang J, Tucholska M, et al. Directed network wiring identifies a key protein interaction in embryonic stem cell differentiation. Mol Cell. 2014;54:1034-41 pubmed publisher
    ..To address this issue, we designed variants of the Grb2 SH2 domain ("pY-clamps") whose specificity is highly biased toward a single phosphotyrosine (pY) motif ..
  82. Su Y, Han J, Xu S, Cobb M, Skolnik E. NIK is a new Ste20-related kinase that binds NCK and MEKK1 and activates the SAPK/JNK cascade via a conserved regulatory domain. EMBO J. 1997;16:1279-90 pubmed
    ..These findings indicate that the C-terminal domain of these proteins encodes a new protein domain family and suggests that this domain couples these kinases to the SAPK pathway, possibly by interacting with MEKK1 or related kinases. ..
  83. Ozaki K, Miyazaki S, Tanimura S, Kohno M. Efficient suppression of FGF-2-induced ERK activation by the cooperative interaction among mammalian Sprouty isoforms. J Cell Sci. 2005;118:5861-71 pubmed
    ..Sprouty1 specifically interacts with Grb2, whereas Sprouty4 interacts with Sos1...