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Gene Review

Gab1  -  growth factor receptor bound protein 2...

Mus musculus

Synonyms: AA408973, AW107238, GRB2-associated binder 1, GRB2-associated-binding protein 1, Growth factor receptor bound protein 2-associated protein 1
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Disease relevance of Gab1


High impact information on Gab1

  • Deletion of Gab1 in the liver leads to enhanced glucose tolerance and improved hepatic insulin action [3].
  • Mice lacking Gab1 die during embryogenesis and show defective responses to several stimuli [4].
  • Here we show that Gab1 interacts directly with the c-met-encoded receptor tyrosine kinase but not with a number of other tyrosine kinases from different subfamilies [5].
  • Thus we have discovered a new phosphotyrosine interaction domain in Gab1 and shown that Gab1 is the substrate of the c-Met receptor tyrosine kinase that mediates epithelial morphogenesis [5].
  • Gab1 encodes an adaptor protein that transduces signals elicited by tyrosine kinase receptors, for instance the c-Met receptor, and plays a role in the migration of muscle progenitor cells [6].

Biological context of Gab1

  • Gab1 is a scaffolding/docking protein that has been suggested to play a role in signal transduction downstream of certain plasma membrane receptors, including platelet-derived growth factor (PDGF) receptors [7].
  • Gab1 acts to diversify the signal downstream from the Met receptor tyrosine kinase through the recruitment of multiple signaling proteins, and is essential for epithelial morphogenesis [8].
  • Gab1 contributes to cytoskeletal reorganization and chemotaxis in response to platelet-derived growth factor [7].
  • The latter requires a novel amino acid sequence present in the Met-binding domain of Gab1 but not Gab2 [8].
  • We demonstrate that, albeit no association is detected between the Tpo receptor mpl and Gab proteins, Y112 located in the C-terminal cytoplasmic domain of mpl is required for Gab1/2 tyrosine phosphorylation [9].

Anatomical context of Gab1


Associations of Gab1 with chemical compounds


Physical interactions of Gab1

  • Gab1 was constitutively complexed with JNK and became tyrosine phosphorylated in UV-irradiated cells [15].

Enzymatic interactions of Gab1


Regulatory relationships of Gab1


Other interactions of Gab1

  • The scaffolding proteins Gab1 and/or Gab2 were candidates for this role [22].
  • We found that CXCR4 and Gab1 interact genetically [6].
  • Furthermore, we showed that the negative role of Gab1 required its Src homology 2-containing tyrosine phosphatase-2 binding sites [23].
  • In isolated murine carotid arteries, flow-induced vasodilatation was prevented by a PKA inhibitor as well as by overexpression of either the YF-Gab1 or the dominant-negative SHP2 mutant [24].
  • RESULTS: We used fibroblasts isolated from Gab1-/- mouse embryos to explore the mechanism of EGF stimulation of the PI-3 kinase/Akt anti-apoptotic cell signaling pathway [25].

Analytical, diagnostic and therapeutic context of Gab1


  1. Adaptor molecule Crk is required for sustained phosphorylation of Grb2-associated binder 1 and hepatocyte growth factor-induced cell motility of human synovial sarcoma cell lines. Watanabe, T., Tsuda, M., Makino, Y., Ichihara, S., Sawa, H., Minami, A., Mochizuki, N., Nagashima, K., Tanaka, S. Mol. Cancer Res. (2006) [Pubmed]
  2. beta1A integrin expression is required for type 1 insulin-like growth factor receptor mitogenic and transforming activities and localization to focal contacts. Goel, H.L., Breen, M., Zhang, J., Das, I., Aznavoorian-Cheshire, S., Greenberg, N.M., Elgavish, A., Languino, L.R. Cancer Res. (2005) [Pubmed]
  3. Deletion of Gab1 in the liver leads to enhanced glucose tolerance and improved hepatic insulin action. Bard-Chapeau, E.A., Hevener, A.L., Long, S., Zhang, E.E., Olefsky, J.M., Feng, G.S. Nat. Med. (2005) [Pubmed]
  4. Essential role for Gab2 in the allergic response. Gu, H., Saito, K., Klaman, L.D., Shen, J., Fleming, T., Wang, Y., Pratt, J.C., Lin, G., Lim, B., Kinet, J.P., Neel, B.G. Nature (2001) [Pubmed]
  5. Interaction between Gab1 and the c-Met receptor tyrosine kinase is responsible for epithelial morphogenesis. Weidner, K.M., Di Cesare, S., Sachs, M., Brinkmann, V., Behrens, J., Birchmeier, W. Nature (1996) [Pubmed]
  6. CXCR4 and Gab1 cooperate to control the development of migrating muscle progenitor cells. Vasyutina, E., Stebler, J., Brand-Saberi, B., Schulz, S., Raz, E., Birchmeier, C. Genes Dev. (2005) [Pubmed]
  7. Gab1 contributes to cytoskeletal reorganization and chemotaxis in response to platelet-derived growth factor. Kallin, A., Demoulin, J.B., Nishida, K., Hirano, T., Rönnstrand, L., Heldin, C.H. J. Biol. Chem. (2004) [Pubmed]
  8. Distinct recruitment and function of Gab1 and Gab2 in Met receptor-mediated epithelial morphogenesis. Lock, L.S., Maroun, C.R., Naujokas, M.A., Park, M. Mol. Biol. Cell (2002) [Pubmed]
  9. Role of Gab proteins in phosphatidylinositol 3-kinase activation by thrombopoietin (Tpo). Bouscary, D., Lecoq-Lafon, C., Chrétien, S., Zompi, S., Fichelson, S., Muller, O., Porteu, F., Dusanter-Fourt, I., Gisselbrecht, S., Mayeux, P., Lacombe, C. Oncogene (2001) [Pubmed]
  10. The docking protein Gab1 is an essential component of an indirect mechanism for fibroblast growth factor stimulation of the phosphatidylinositol 3-kinase/Akt antiapoptotic pathway. Lamothe, B., Yamada, M., Schaeper, U., Birchmeier, W., Lax, I., Schlessinger, J. Mol. Cell. Biol. (2004) [Pubmed]
  11. The absence of Grb2-associated binder 2 (Gab2) does not disrupt NK cell development and functions. Zompi, S., Gu, H., Colucci, F. J. Leukoc. Biol. (2004) [Pubmed]
  12. Development of an efficient "substrate-trapping" mutant of Src homology phosphotyrosine phosphatase 2 and identification of the epidermal growth factor receptor, Gab1, and three other proteins as target substrates. Agazie, Y.M., Hayman, M.J. J. Biol. Chem. (2003) [Pubmed]
  13. Src-family tyrosine kinases, phosphoinositide 3-kinase and Gab1 regulate extracellular signal-regulated kinase 1 activation induced by the type A endothelin-1 G-protein-coupled receptor. Bisotto, S., Fixman, E.D. Biochem. J. (2001) [Pubmed]
  14. Gab1 is an integrator of cell death versus cell survival signals in oxidative stress. Holgado-Madruga, M., Wong, A.J. Mol. Cell. Biol. (2003) [Pubmed]
  15. Role of Gab1 in UV-induced c-Jun NH2-terminal kinase activation and cell apoptosis. Sun, Y., Yuan, J., Liu, H., Shi, Z., Baker, K., Vuori, K., Wu, J., Feng, G.S. Mol. Cell. Biol. (2004) [Pubmed]
  16. The osmotic shock-induced glucose transport pathway in 3T3-L1 adipocytes is mediated by gab-1 and requires Gab-1-associated phosphatidylinositol 3-kinase activity for full activation. Janez, A., Worrall, D.S., Imamura, T., Sharma, P.M., Olefsky, J.M. J. Biol. Chem. (2000) [Pubmed]
  17. Distinct requirements for Gab1 in Met and EGF receptor signaling in vivo. Schaeper, U., Vogel, R., Chmielowiec, J., Huelsken, J., Rosario, M., Birchmeier, W. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  18. Concerted functions of Gab1 and Shp2 in liver regeneration and hepatoprotection. Bard-Chapeau, E.A., Yuan, J., Droin, N., Long, S., Zhang, E.E., Nguyen, T.V., Feng, G.S. Mol. Cell. Biol. (2006) [Pubmed]
  19. Roles of cell-cell adhesion-dependent tyrosine phosphorylation of Gab-1. Shinohara, M., Kodama, A., Matozaki, T., Fukuhara, A., Tachibana, K., Nakanishi, H., Takai, Y. J. Biol. Chem. (2001) [Pubmed]
  20. A switch from p130Cas/Crk to Gab1/Crk signaling correlates with anchorage independent growth and JNK activation in cells transformed by the Met receptor oncoprotein. Lamorte, L., Kamikura, D.M., Park, M. Oncogene (2000) [Pubmed]
  21. Gab-1-mediated IGF-1 signaling in IRS-1-deficient 3T3 fibroblasts. Winnay, J.N., Brüning, J.C., Burks, D.J., Kahn, C.R. J. Biol. Chem. (2000) [Pubmed]
  22. Scaffolding protein Gab2 mediates fibroblast transformation by the SEA tyrosine kinase. Ischenko, I., Petrenko, O., Gu, H., Hayman, M.J. Oncogene (2003) [Pubmed]
  23. Adapter molecule Grb2-associated binder 1 is specifically expressed in marginal zone B cells and negatively regulates thymus-independent antigen-2 responses. Itoh, S., Itoh, M., Nishida, K., Yamasaki, S., Yoshida, Y., Narimatsu, M., Park, S.J., Hibi, M., Ishihara, K., Hirano, T. J. Immunol. (2002) [Pubmed]
  24. Gab1, SHP2, and protein kinase A are crucial for the activation of the endothelial NO synthase by fluid shear stress. Dixit, M., Loot, A.E., Mohamed, A., Fisslthaler, B., Boulanger, C.M., Ceacareanu, B., Hassid, A., Busse, R., Fleming, I. Circ. Res. (2005) [Pubmed]
  25. The docking protein Gab1 is the primary mediator of EGF-stimulated activation of the PI-3K/Akt cell survival pathway. Mattoon, D.R., Lamothe, B., Lax, I., Schlessinger, J. BMC Biol. (2004) [Pubmed]
  26. Role of Gab1 in heart, placenta, and skin development and growth factor- and cytokine-induced extracellular signal-regulated kinase mitogen-activated protein kinase activation. Itoh, M., Yoshida, Y., Nishida, K., Narimatsu, M., Hibi, M., Hirano, T. Mol. Cell. Biol. (2000) [Pubmed]
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