Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Gab1

  • Richard Vaillancourt
  • Annina C. Spilker
  • Morag Park
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_340

Historical Background

Gab proteins are scaffold proteins that are related to the insulin receptor substrates (IRS1/2/3), the fibroblast growth factor ( FGF) receptor substrate 2 (FRS2-α/β), the downstream of kinase (Dok), and the linker of T cell ( LAT). These proteins lack intrinsic enzymatic activity. Upon their recruitment to activated growth factor and cytokine receptors, they become tyrosine phosphorylated, providing binding sites for multiple proteins involved in signal transduction. By virtue of their ability to assemble multiprotein complexes, they act to modulate, amplify, and diversify the signals downstream from receptors (Pawson and Scott 1997; Schlessinger and Lemmon 2003).

The Gab family comprises three mammalian members, Gab1, Gab2, Gab3 (Fig. 1), the Drosophila melanogaster DOS (daughter of sevenless), and the Caenorhabditis elegansSOC-1. Gab1 was first identified in a screen for Grb2 binding proteins and was found to be a substrate for the EGF, TrkA, and insulin...
This is a preview of subscription content, log in to check access.

References

  1. Abella JV, Vaillancourt R, Frigault MM, Ponzo MG, Zuo D, Sangwan V, Larose L, Park M. The Gab1 scaffold regulates RTK-dependent dorsal ruffle formation through the adaptor Nck. J Cell Sci. 2010;123:1306–19.PubMedCrossRefGoogle Scholar
  2. Birchmeier C, Birchmeier W, Gherardi E, Vande Woude GF. Met, metastasis, motility and more. Nat Rev Mol Cell Biol. 2003;4:915–25.PubMedCrossRefGoogle Scholar
  3. Eswarakumar VP, Lax I, Schlessinger J. Cellular signaling by fibroblast growth factor receptors. Cytokine Growth Factor Rev. 2005;16:139–49.PubMedCrossRefGoogle Scholar
  4. Gillgrass A, Cardiff RD, Sharan N, Kannan S, Muller WJ. Epidermal growth factor receptor-dependent activation of Gab1 is involved in ErbB-2-mediated mammary tumor progression. Oncogene. 2003;22:9151–5.PubMedCrossRefGoogle Scholar
  5. Gu H, Neel BG. The “Gab” in signal transduction. Trends Cell Biol. 2003;13:122–30.PubMedCrossRefGoogle Scholar
  6. Lamorte L, Kamikura DM, Park M. 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. Oncogene. 2000;19:5973–81.PubMedCrossRefGoogle Scholar
  7. Laramee M, Chabot C, Cloutier M, Stenne R, Holgado-Madruga M, Wong AJ, Royal I. The scaffolding adapter Gab1 mediates vascular endothelial growth factor signaling and is required for endothelial cell migration and capillary formation. J Biol Chem. 2007;282:7758–69.PubMedCrossRefGoogle Scholar
  8. Liu Y, Rohrschneider LR. The gift of Gab. FEBS Lett. 2002;515:1–7.PubMedCrossRefGoogle Scholar
  9. Maeda K, Murakami H, Yoshida R, Ichihara M, Abe A, Hirai M, Murohara T, Takahashi M. Biochemical and biological responses induced by coupling of Gab1 to phosphatidylinositol 3-kinase in RET-expressing cells. Biochem Biophys Res Commun. 2004;323:345–54.PubMedCrossRefGoogle Scholar
  10. Nishida K, Hirano T. The role of Gab family scaffolding adapter proteins in the signal transduction of cytokine and growth factor receptors. Cancer Sci. 2003;94:1029–33.PubMedCrossRefGoogle Scholar
  11. Oka M, Kikkawa U, Nishigori C. Protein kinase C-betaII represses hepatocyte growth factor-induced invasion by preventing the association of adapter protein Gab1 and phosphatidylinositol 3-kinase in melanoma cells. J Invest Dermatol. 2008;128:188–95.PubMedCrossRefGoogle Scholar
  12. Paliouras GN, Naujokas MA, Park M. Pak4, a novel Gab1 binding partner, modulates cell migration and invasion by the Met receptor. Mol Cell Biol. 2009;29:3018–32.PubMedPubMedCentralCrossRefGoogle Scholar
  13. Pawson T, Scott JD. Signaling through scaffold, anchoring, and adaptor proteins. Science. 1997;278:2075–80.PubMedCrossRefGoogle Scholar
  14. Peschard P, Park M. From Tpr-Met to Met, tumorigenesis and tubes. Oncogene. 2007;26:1276–85.PubMedCrossRefGoogle Scholar
  15. Rodrigues GA, Falasca M, Zhang Z, Ong SH, Schlessinger J. A novel positive feedback loop mediated by the docking protein Gab1 and phosphatidylinositol 3-kinase in epidermal growth factor receptor signaling. Mol Cell Biol. 2000;20:1448–59.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Sarmay G, Angyal A, Kertesz A, Maus M, Medgyesi D. The multiple function of Grb2 associated binder (Gab) adaptor/scaffolding protein in immune cell signaling. Immunol Lett. 2006;104:76–82.PubMedCrossRefGoogle Scholar
  17. Schaeper U, Vogel R, Chmielowiec J, Huelsken J, Rosario M, Birchmeier W. Distinct requirements for Gab1 in Met and EGF receptor signaling in vivo. Proc Natl Acad Sci USA. 2007;104:15376–81.PubMedPubMedCentralCrossRefGoogle Scholar
  18. Schlessinger J, Lemmon MA. SH2 and PTB domains in tyrosine kinase signaling. Sci STKE. 2003;2003:RE12.PubMedGoogle Scholar
  19. Seiden-Long I, Navab R, Shih W, Li M, Chow J, Zhu CQ, Radulovich N, Saucier C, Tsao MS. Gab1 but not Grb2 mediates tumor progression in Met overexpressing colorectal cancer cells. Carcinogenesis. 2008;29:647–55.PubMedCrossRefGoogle Scholar
  20. Turke AB, Zejnullahu K, YL W, Song Y, Dias-Santagata D, Lifshits E, Toschi L, Rogers A, Mok T, Sequist L, et al. Preexistence and clonal selection of MET amplification in EGFR mutant NSCLC. Cancer Cell. 2010;17:77–88.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Wohrle FU, Daly RJ, Brummer T. Function, regulation and pathological roles of the Gab/DOS docking proteins. Cell Commun Signal. 2009;7:22.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Richard Vaillancourt
    • 1
    • 2
  • Annina C. Spilker
    • 1
    • 2
  • Morag Park
    • 1
    • 2
    • 3
    • 4
  1. 1.Goodman Cancer Research CentreMcGill UniversityMontréalCanada
  2. 2.Department of BiochemistryMcGill UniversityMontréalCanada
  3. 3.Department of MedicineMcGill UniversityMontréalCanada
  4. 4.Department of OncologyMcGill UniversityMontréalCanada