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

Top Publications

  1. Park R, Kim D, Kim M, So H, Chung H, Kwon K, et al. Association of Shc, Cbl, Grb2, and Sos following treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin in primary rat hepatocytes. Biochem Biophys Res Commun. 1998;253:577-81 pubmed
    ..The present study is designed to clarify whether TCDD modulates the molecular interactions of Shc, Cbl, Grb2, and Sos in primary rat hepatocytes...
  2. Gupta V, You Y, Gupta V, Klistorner A, Graham S. TrkB receptor signalling: implications in neurodegenerative, psychiatric and proliferative disorders. Int J Mol Sci. 2013;14:10122-42 pubmed publisher
    ..In this review, we discuss the mechanisms underlying TrkB signalling, disease implications and explore plausible ameliorative or preventive approaches. ..
  3. Tashiro K, Tsunematsu T, Okubo H, Ohta T, Sano E, Yamauchi E, et al. GAREM, a novel adaptor protein for growth factor receptor-bound protein 2, contributes to cellular transformation through the activation of extracellular signal-regulated kinase signaling. J Biol Chem. 2009;284:20206-14 pubmed publisher
    ..Here, we focus on a novel protein, GAREM (Grb2-associated and regulator of Erk/MAPK) as a downstream molecule of the EGF receptor...
  4. Lin Q, Wang J, Childress C, Sudol M, Carey D, Yang W. HECT E3 ubiquitin ligase Nedd4-1 ubiquitinates ACK and regulates epidermal growth factor (EGF)-induced degradation of EGF receptor and ACK. Mol Cell Biol. 2010;30:1541-54 pubmed publisher
    ..Our findings suggest an essential role of Nedd4-1 in regulation of EGFR degradation through interaction with and ubiquitination of ACK. ..
  5. Birchmeier C, Birchmeier W, Gherardi E, Vande Woude G. Met, metastasis, motility and more. Nat Rev Mol Cell Biol. 2003;4:915-25 pubmed
  6. Wang Y, Zhu Y, Zhang L, Tian W, Hua S, Zhao J, et al. Insulin promotes proliferation, survival, and invasion in endometrial carcinoma by activating the MEK/ERK pathway. Cancer Lett. 2012;322:223-31 pubmed publisher
    ..Serum levels of insulin, p-p52Shc, p-p46Shc, Shc·Grb2 complexes, p-MEK, p-ERK, and cyclin D1 were elevated in patients with EC...
  7. Hunter S, Koch B, Anderson S. Phosphorylation of cbl after stimulation of Nb2 cells with prolactin and its association with phosphatidylinositol 3-kinase. Mol Endocrinol. 1997;11:1213-22 pubmed
    ..The cbl protein appears to be constitutively associated with grb2 and the p85 subunit of phosphatidylinositol 3-kinase (PI 3-kinase)...
  8. Newton S, Collier E, Bennett A, Russell D, Duman R. Regulation of growth factor receptor bound 2 by electroconvulsive seizure. Brain Res Mol Brain Res. 2004;129:185-8 pubmed
    ..In this context, we examined the regulation of growth factor receptor bound 2 (Grb2), an important adaptor molecule in several growth factor signaling cascades...
  9. Harita Y, Kurihara H, Kosako H, Tezuka T, Sekine T, Igarashi T, et al. Neph1, a component of the kidney slit diaphragm, is tyrosine-phosphorylated by the Src family tyrosine kinase and modulates intracellular signaling by binding to Grb2. J Biol Chem. 2008;283:9177-86 pubmed publisher
    ..In pull-down assays using rat glomerular lysates, Neph1 but not nephrin specifically binds to adaptor protein Grb2 and tyrosine kinase Csk in a phosphorylation-dependent manner...

More Information


  1. Mincione G, Esposito D, Di Marcantonio M, Piccirelli A, Cama A, Colletta G. TGF-beta 1 modulation of IGF-I signaling pathway in rat thyroid epithelial cells. Exp Cell Res. 2003;287:411-23 pubmed
    ..1 affected IGF-I-stimulated insulin receptor substrate 1 (IRS-1) tyrosine phosphorylation and its association with Grb2 protein...
  2. Huang F, Khvorova A, Marshall W, Sorkin A. Analysis of clathrin-mediated endocytosis of epidermal growth factor receptor by RNA interference. J Biol Chem. 2004;279:16657-61 pubmed
    ..Thus, CALM is the second protein besides Grb2 that appears to play a specific role in EGFR endocytosis...
  3. Jackman J, Motto D, Sun Q, Tanemoto M, Turck C, Peltz G, et al. Molecular cloning of SLP-76, a 76-kDa tyrosine phosphoprotein associated with Grb2 in T cells. J Biol Chem. 1995;270:7029-32 pubmed
    ..TCR-activated protein tyrosine kinase pathway is a 76-kDa protein (pp76) that associates with the adaptor protein Grb2. In this report we describe the purification of pp76 and the molecular cloning of its cDNA, which encodes a novel ..
  4. Chu J, Liu Y, Koretzky G, Durden D. SLP-76-Cbl-Grb2-Shc interactions in FcgammaRI signaling. Blood. 1998;92:1697-706 pubmed
    ..Cbl, and Shc are tyrosine phosphorylated on FcgammaRI-receptor stimulation and are associated with the adapter protein Grb2 in gamma-interferon-differentiated U937 cells (U937IF)...
  5. Lin X, Gu Y, Kapoor A, Wei F, Aziz T, Ojo D, et al. Overexpression of MUC1 and Genomic Alterations in Its Network Associate with Prostate Cancer Progression. Neoplasia. 2017;19:857-867 pubmed publisher
    ..nine-gene signature was derived, including eight genes from a MUC1-related network (APC, CTNNB1/?-catenin, GALNT10, GRB2, LYN, SIGLEC1, SOS1, and ZAP70) and FAM84B...
  6. Liu F, Hill D, Chernoff J. Direct binding of the proline-rich region of protein tyrosine phosphatase 1B to the Src homology 3 domain of p130(Cas). J Biol Chem. 1996;271:31290-5 pubmed
    ..In this study, we establish that PTP1B interacts with Crk, Grb2, and p130(Cas) in vitro and with at least one of these, p130(Cas), in intact cells...
  7. Watanabe K, Fukuchi T, Hosoya H, Shirasawa T, Matuoka K, Miki H, et al. Splicing isoforms of rat Ash/Grb2. Isolation and characterization of the cDNA and genomic DNA clones and implications for the physiological roles of the isoforms. J Biol Chem. 1995;270:13733-9 pubmed
    We obtained three types of cDNA clones homologous to Ash/Grb2(Ash-l) cDNA from rats. One of these clones, Ash-psi, was an unusual transcribed gene having 93% identity in the nucleotide sequence to Ash-l...
  8. Shinoda T, Taya S, Tsuboi D, Hikita T, Matsuzawa R, Kuroda S, et al. DISC1 regulates neurotrophin-induced axon elongation via interaction with Grb2. J Neurosci. 2007;27:4-14 pubmed
    ..Here we identified growth factor receptor bound protein 2 (Grb2) as a novel DISC1-interacting molecule...
  9. 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...
  10. Sasaoka T, Langlois W, Leitner J, Draznin B, Olefsky J. The signaling pathway coupling epidermal growth factor receptors to activation of p21ras. J Biol Chem. 1994;269:32621-5 pubmed
    ..The connection of the EGFR to p21ras activation can occur through binding of Grb2.Sos complexes to the EGFR or through the adaptor protein Shc via EGFR.Shc.Grb2.Sos multimeric complexes...
  11. Manu M, Rachana K, Advirao G. Altered expression of IRS2 and GRB2 in demyelination of peripheral neurons: Implications in diabetic neuropathy. Neuropeptides. 2017;62:71-79 pubmed publisher
    ..receptor substrate-1 (IRS1), insulin receptor substrate-2 (IRS2) and growth factor receptor-bound protein-2 (GRB2) that propagate the insulin signaling and also their variation in hyperglycemic SCs and sciatic nerve of the ..
  12. Zucconi A, Dente L, Santonico E, Castagnoli L, Cesareni G. Selection of ligands by panning of domain libraries displayed on phage lambda reveals new potential partners of synaptojanin 1. J Mol Biol. 2001;307:1329-39 pubmed
    ..Two different proline-rich regions of the p21-activated protein kinase 1 (Pak1) and WAVE/SCAR2 protein retrieve from the library different proteins containing SH3 or WW domains. ..
  13. Rottapel R, Turck C, Casteran N, Liu X, Birnbaum D, Pawson T, et al. Substrate specificities and identification of a putative binding site for PI3K in the carboxy tail of the murine Flt3 receptor tyrosine kinase. Oncogene. 1994;9:1755-65 pubmed
    ..FF3 associates with PI3K activity and the SH2 domains of p85 and Grb-2. Phosphopeptide competition experiments suggest that the PI3K binding site is located outside of the kinase insert in the carboxy tail of the receptor. ..
  14. Poy M, Ruch R, Fernstrom M, Okabayashi Y, Najjar S. Shc and CEACAM1 interact to regulate the mitogenic action of insulin. J Biol Chem. 2002;277:1076-84 pubmed
    ..Thus, by binding to Shc, CEACAM1 sequesters this major coupler of Grb2 to the insulin receptor and down-regulates the Ras/MAP kinase mitogenesis pathway...
  15. Anggono V, Robinson P. Syndapin I and endophilin I bind overlapping proline-rich regions of dynamin I: role in synaptic vesicle endocytosis. J Neurochem. 2007;102:931-43 pubmed
    ..We propose syndapin and endophilin function either at different stages during SVE or in mechanistically distinct types of SVE. ..
  16. Hamazaki T, Kehoe S, Nakano T, Terada N. The Grb2/Mek pathway represses Nanog in murine embryonic stem cells. Mol Cell Biol. 2006;26:7539-49 pubmed
    ..The effects of sodium vanadate were abrogated by Grb2 deficiency or by the addition of the Mek inhibitor, PD98059...
  17. 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 ..
  18. Kong M, Mounier C, Wu J, Posner B. Epidermal growth factor-induced phosphatidylinositol 3-kinase activation and DNA synthesis. Identification of Grb2-associated binder 2 as the major mediator in rat hepatocytes. J Biol Chem. 2000;275:36035-42 pubmed
    ..PY105 associated with Grb2 and SHP-2, and although it behaved like Gab1, none of the latter was detected in rat liver...
  19. Ahmed Z, Timsah Z, Suen K, Cook N, Lee G, Lin C, et al. Grb2 monomer-dimer equilibrium determines normal versus oncogenic function. Nat Commun. 2015;6:7354 pubmed publisher
    The adaptor protein growth factor receptor-bound protein 2 (Grb2) is ubiquitously expressed in eukaryotic cells and involved in a multitude of intracellular protein interactions...
  20. Passos J, Nelson G, Wang C, Richter T, Simillion C, Proctor C, et al. Feedback between p21 and reactive oxygen production is necessary for cell senescence. Mol Syst Biol. 2010;6:347 pubmed publisher
    ..and production of reactive oxygen species (ROS) through serial signalling through GADD45-MAPK14(p38MAPK)-GRB2-TGFBR2-TGFbeta. These ROS in turn replenish short-lived DNA damage foci and maintain an ongoing DDR...
  21. Dadke S, Chernoff J. Interaction of protein tyrosine phosphatase (PTP) 1B with its substrates is influenced by two distinct binding domains. Biochem J. 2002;364:377-83 pubmed
    ..These data show that PTP1B can independently regulate insulin and integrin signals, and that Src might represent a convergence point for regulating signal transduction by this phosphatase. ..
  22. 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 ..
  23. Ishihara H, Sasaoka T, Ishiki M, Takata Y, Imamura T, Usui I, et al. Functional importance of Shc tyrosine 317 on insulin signaling in Rat1 fibroblasts expressing insulin receptors. J Biol Chem. 1997;272:9581-6 pubmed
    Shc is phosphorylated on Tyr-317, which serves as a docking site for Grb2. To investigate the specific role of Shc phosphorylation and Shc...
  24. 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...
  25. Gril B, Vidal M, Assayag F, Poupon M, Liu W, Garbay C. Grb2-SH3 ligand inhibits the growth of HER2+ cancer cells and has antitumor effects in human cancer xenografts alone and in combination with docetaxel. Int J Cancer. 2007;121:407-15 pubmed
    ..Thus, new therapeutic approaches to the HER2 pathway are needed. Grb2 is an adaptor protein involved in Ras-dependent signaling induced by HER2 receptors...
  26. 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. ..
  27. Gentile A, Trusolino L, Comoglio P. The Met tyrosine kinase receptor in development and cancer. Cancer Metastasis Rev. 2008;27:85-94 pubmed publisher
    ..Several approaches have been recently developed to interfere with the tumorigenic and metastatic processes triggered by Met. ..
  28. Hayashi K, Shibata K, Morita T, Iwasaki K, Watanabe M, Sobue K. Insulin receptor substrate-1/SHP-2 interaction, a phenotype-dependent switching machinery of insulin-like growth factor-I signaling in vascular smooth muscle cells. J Biol Chem. 2004;279:40807-18 pubmed
    ..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...
  29. Tanase C. Histidine domain-protein tyrosine phosphatase interacts with Grb2 and GrpL. PLoS ONE. 2010;5:e14339 pubmed publisher
    ..In this study we performed a yeast two-hybrid screening using a human colon cDNA library and found that Grb2 and GrpL are binding partners of HD-PTP...
  30. Tobe K, Matuoka K, Tamemoto H, Ueki K, Kaburagi Y, Asai S, et al. Insulin stimulates association of insulin receptor substrate-1 with the protein abundant Src homology/growth factor receptor-bound protein 2. J Biol Chem. 1993;268:11167-71 pubmed
    ..The protein ASH (for abundant Src homology) (Matuoka, K., Shibata, M., Yamakawa, A., and Takenawa, T. (1992) Proc. Natl. Acad...
  31. Maru Y, Afar D, Witte O, Shibuya M. The dimerization property of glutathione S-transferase partially reactivates Bcr-Abl lacking the oligomerization domain. J Biol Chem. 1996;271:15353-7 pubmed
    ..The Grb-2 binding to GST/Bcr-Abl-(Delta1-160) was 50% reduced in Rat1 cells and undetectable in Ba/F3 cells. In Rat1 cells expressing GST/Bcr-Abl-(Delta1-160), phosphotyrosine contents of p62 and Shc were 70% decreased. ..
  32. Mihara M, Hashizume M, Yoshida H, Suzuki M, Shiina M. IL-6/IL-6 receptor system and its role in physiological and pathological conditions. Clin Sci (Lond). 2012;122:143-59 pubmed publisher
    ..In the present review, we first summarize the IL-6/IL-6R system and IL-6 signal transduction, and then go on to discuss the physiological and pathological roles of IL-6. ..
  33. Xia Y, Sheng J, Liang G, Liu D, Tang Q, Cheng A. miR-96 inhibits cardiac hypertrophy by targeting growth factor receptor-bound 2. Genet Mol Res. 2015;14:18958-64 pubmed publisher
    ..Our data demonstrate that miR-96 is a negative regulator of cardiac hypertrophy and extracellular-regulated protein kinase signaling, thus offering a new therapeutic strategy for cardiac hypertrophy. ..
  34. Xie Y, Wang Y, Sun T, Wang F, Trostinskaia A, Puscheck E, et al. Six post-implantation lethal knockouts of genes for lipophilic MAPK pathway proteins are expressed in preimplantation mouse embryos and trophoblast stem cells. Mol Reprod Dev. 2005;71:1-11 pubmed
    ..These included FRS2alpha, GAB1, GRB2, SOS1, Raf-B, and Raf1...
  35. Chadwick W, Keselman A, Park S, Zhou Y, Wang L, Brenneman R, et al. Repetitive peroxide exposure reveals pleiotropic mitogen-activated protein kinase signaling mechanisms. J Signal Transduct. 2011;2011:636951 pubmed publisher
    ..Our data indicates that components of peroxide-induced ERK1/2 cascades are differentially affected by repeated exposures, indicating that oxidative signaling may be contextually variable. ..
  36. Panchamoorthy G, Fukazawa T, Miyake S, Soltoff S, Reedquist K, Druker B, et al. p120cbl is a major substrate of tyrosine phosphorylation upon B cell antigen receptor stimulation and interacts in vivo with Fyn and Syk tyrosine kinases, Grb2 and Shc adaptors, and the p85 subunit of phosphatidylinositol 3-kinase. J Biol Chem. 1996;271:3187-94 pubmed
    ..A substantial fraction of Cbl was constitutively associated with Grb2 and this interaction was mediated by Grb2 SH3 domains...
  37. Russo C, Dolcini V, Salis S, Venezia V, Zambrano N, Russo T, et al. 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. J Biol Chem. 2002;277:35282-8 pubmed
    ..b>Grb2 is also part of these complexes, which are present in higher amounts in AD than in control brains...
  38. McDonald C, Bhat V, Mikles D, Deegan B, Seldeen K, Farooq A. Bivalent binding drives the formation of the Grb2-Gab1 signaling complex in a noncooperative manner. FEBS J. 2012;279:2156-73 pubmed publisher
    Although the growth factor receptor binder 2 (Grb2)-Grb2-associated binder (Gab)1 macromolecular complex mediates a multitude of cellular signaling cascades, the molecular basis of its assembly has hitherto remained largely elusive...
  39. Dankort D, Wang Z, Blackmore V, Moran M, Muller W. Distinct tyrosine autophosphorylation sites negatively and positively modulate neu-mediated transformation. Mol Cell Biol. 1997;17:5410-25 pubmed
    ..signaling, the transforming activity of two of these mutants was correlated with their ability to bind either the GRB2 or SHC adapter molecules that couple receptor tyrosine kinases to the Ras signaling pathway...
  40. Matuoka K, Shibata M, Yamakawa A, Takenawa T. Cloning of ASH, a ubiquitous protein composed of one Src homology region (SH) 2 and two SH3 domains, from human and rat cDNA libraries. Proc Natl Acad Sci U S A. 1992;89:9015-9 pubmed
    The protein ASH (for abundant Src homology), composed of one Src homology region (SH) 2 and two SH3 domains, was cloned by screening human and rat cDNA libraries with an oligonucleotide probe directed to a consensus sequence of the SH2 ..
  41. Dikic I, Schlessinger J, Lax I. PC12 cells overexpressing the insulin receptor undergo insulin-dependent neuronal differentiation. Curr Biol. 1994;4:702-8 pubmed
    ..pattern of insulin-induced tyrosine-phosphorylated proteins in PC12 cells, including enhanced recruitment of Grb2/Sos into a complex with either Shc or IRS1...
  42. Chen Hwang M, Chen H, Elzinga M, Hwang Y. Dynamin is a minibrain kinase/dual specificity Yak1-related kinase 1A substrate. J Biol Chem. 2002;277:17597-604 pubmed
    ..the interaction of dynamin with endophilin 1, whereas the same phosphorylation enhanced the binding of dynamin 1 to Grb2. Nevertheless, the dual function of Mnbk/Dyrk1A phosphorylation was not observed for the interaction of dynamin 1 ..
  43. Ge S, Xiong Y, Wu X, Xie J, Liu F, He J, et al. Role of growth factor receptor-bound 2 in CCl4-induced hepatic fibrosis. Biomed Pharmacother. 2017;92:942-951 pubmed publisher
    Growth Factor Receptor-bound 2 (GRB2) plays a crucial role in regulation of cellular function including proliferation and differentiation, and we previously identified GRB2 as promoting HSCs (HSCs) proliferation...
  44. Tacconelli A, Farina A, Cappabianca L, Desantis G, Tessitore A, Vetuschi A, et al. TrkA alternative splicing: a regulated tumor-promoting switch in human neuroblastoma. Cancer Cell. 2004;6:347-60 pubmed
  45. 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...
  46. Howard P, Chia M, Del Rizzo S, Liu F, Pawson T. Redirecting tyrosine kinase signaling to an apoptotic caspase pathway through chimeric adaptor proteins. Proc Natl Acad Sci U S A. 2003;100:11267-72 pubmed
    ..Receptor tyrosine kinases (RTKs) recruit adaptors, such as Grb2 and ShcA, that activate signaling pathways involved in growth and survival, whereas death receptors bind adaptors, ..
  47. Carvalheira J, Calegari V, Zecchin H, Nadruz W, Guimarães R, Ribeiro E, et al. The cross-talk between angiotensin and insulin differentially affects phosphatidylinositol 3-kinase- and mitogen-activated protein kinase-mediated signaling in rat heart: implications for insulin resistance. Endocrinology. 2003;144:5604-14 pubmed
    ..Thus, the imbalance between PI 3-kinase-Akt and MAPK signaling pathways in the heart may play a role in the development of cardiovascular abnormalities observed in insulin-resistant states, such as in obese Zucker rats. ..
  48. Nemoto Y, Wenk M, Watanabe M, Daniell L, Murakami T, Ringstad N, et al. Identification and characterization of a synaptojanin 2 splice isoform predominantly expressed in nerve terminals. J Biol Chem. 2001;276:41133-42 pubmed
    ..These results suggest that synaptojanin 2B has a partially overlapping function with synaptojanin 1 in nerve terminals, with additional roles in neurons and other cells including spermatids. ..
  49. Guo Q, Gao Y, Cong L. [Effects of free fatty acids on insulin signaling proteins in rat islet cells]. Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2002;18:283-6 pubmed
    ..mmol/L) for 12 hours, 24 hours and 36 hours, western bolt was used to assess the protein abundance of cPKCalpha, Grb2 and FERK2...
  50. Dalle S, Imamura T, Rose D, Worrall D, Ugi S, Hupfeld C, et al. Insulin induces heterologous desensitization of G-protein-coupled receptor and insulin-like growth factor I signaling by downregulating beta-arrestin-1. Mol Cell Biol. 2002;22:6272-85 pubmed
  51. Salcini A, McGlade J, Pelicci G, Nicoletti I, Pawson T, Pelicci P. Formation of Shc-Grb2 complexes is necessary to induce neoplastic transformation by overexpression of Shc proteins. Oncogene. 1994;9:2827-36 pubmed
    ..Phosphorylated Shc proteins form a complex with the SH2-SH3 containing Grb2 protein which is implicated in the regulation of Ras, suggesting that Shc is involved in the intracellular ..
  52. 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...
  53. Satoh S, Tominaga T. mDia-interacting protein acts downstream of Rho-mDia and modifies Src activation and stress fiber formation. J Biol Chem. 2001;276:39290-4 pubmed
    ..The new protein mainly binds to the proline-rich region of mDia through its Src homology 3 domain and also binds to Grb2 through its proline-rich domain...
  54. Lin C, Melo F, Ghosh R, Suen K, Stagg L, Kirkpatrick J, et al. Inhibition of basal FGF receptor signaling by dimeric Grb2. Cell. 2012;149:1514-24 pubmed publisher
    ..Here a mechanism is described in which control of FGFR2 activation is provided by the adaptor protein Grb2. Dimeric Grb2 binds to the C termini of two FGFR2 molecules...
  55. Soltoff S. Related adhesion focal tyrosine kinase and the epidermal growth factor receptor mediate the stimulation of mitogen-activated protein kinase by the G-protein-coupled P2Y2 receptor. Phorbol ester or [Ca2+]i elevation can substitute for receptor activat. J Biol Chem. 1998;273:23110-7 pubmed
    ..for the EGF receptor, reduced the activation of MAP kinase, the tyrosine phosphorylation of SHC, the association of Grb2 with SHC, and the tyrosine phosphorylation of the EGF receptor and p120(cbl) but did not block the tyrosine ..
  56. Wigge P, Vallis Y, McMahon H. Inhibition of receptor-mediated endocytosis by the amphiphysin SH3 domain. Curr Biol. 1997;7:554-60 pubmed
    ..Amphiphysin, a protein that is highly expressed in the brain, interacts with dynamin in vitro, as do Grb2 and many other SH3 domain-containing proteins...
  57. Benesch S, Lommel S, Steffen A, Stradal T, Scaplehorn N, Way M, et al. Phosphatidylinositol 4,5-biphosphate (PIP2)-induced vesicle movement depends on N-WASP and involves Nck, WIP, and Grb2. J Biol Chem. 2002;277:37771-6 pubmed the tips of actin comets involved the recruitment of the Src homology 3 (SH3)-SH2 adaptor proteins Nck and Grb2 as well as of WASP interacting protein (WIP)...
  58. Piiper A, Dikic I, Lutz M, Leser J, Kronenberger B, Elez R, et al. Cyclic AMP induces transactivation of the receptors for epidermal growth factor and nerve growth factor, thereby modulating activation of MAP kinase, Akt, and neurite outgrowth in PC12 cells. J Biol Chem. 2002;277:43623-30 pubmed
  59. Skolnik E, Batzer A, Li N, Lee C, Lowenstein E, Mohammadi M, et al. The function of GRB2 in linking the insulin receptor to Ras signaling pathways. Science. 1993;260:1953-5 pubmed
    ..insulin-induced activation of ERKs was enhanced by stable overexpression of growth factor receptor-bound protein 2 (GRB2) but not by overexpression of GRB2 proteins with point mutations in the Src homology 2 and 3 domains...
  60. 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 ..
  61. Murata Y, Mori M, Kotani T, Supriatna Y, Okazawa H, Kusakari S, et al. Tyrosine phosphorylation of R3 subtype receptor-type protein tyrosine phosphatases and their complex formations with Grb2 or Fyn. Genes Cells. 2010;15:513-24 pubmed publisher
    ..Src family kinases are important for the tyrosine phosphorylation of SAP-1. Either Grb2 or Fyn, through their Src homology-2 domains, bound to the tyrosine-phosphorylated SAP-1...
  62. Houdart F, Girard Nau N, Morin F, Voisin P, Vannier B. The regulatory subunit of PDE6 interacts with PACSIN in photoreceptors. Mol Vis. 2005;11:1061-70 pubmed
    ..The description of this new function of PDE6gamma might help to understand the molecular mechanism of the severe retinal degeneration observed in PDE6gamma knock-out mice. ..
  63. Citri A, Yarden Y. EGF-ERBB signalling: towards the systems level. Nat Rev Mol Cell Biol. 2006;7:505-16 pubmed
    ..Because network fragility is an inevitable trade-off of robustness, systems-level understanding is expected to generate therapeutic opportunities to intercept aberrant network activation. ..
  64. Khamzina L, Gruppuso P, Wands J. Insulin signaling through insulin receptor substrate 1 and 2 in normal liver development. Gastroenterology. 2003;125:572-85 pubmed
    ..However, insulin-mediated IRS-1/MAPK cascade activation contributes to growth in the adult. ..
  65. MacDonald J, Gryz E, Kubu C, Verdi J, Meakin S. Direct binding of the signaling adapter protein Grb2 to the activation loop tyrosines on the nerve growth factor receptor tyrosine kinase, TrkA. J Biol Chem. 2000;275:18225-33 pubmed
    We demonstrate that the signaling adapter, Grb2, binds directly to the neurotrophin receptor tyrosine kinase, TrkA...