Understanding the Brain


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GRB2-associated-binding protein 2 is a protein that in humans is encoded by the GAB2 gene.[1][2][3]

The protein encoded by this gene, GAB2 is an adaptor protein serving as principal activator of Phosphatidylinositol 3-kinase. 10 SNPs of GAB2 gene have been found in one study to associate with risk of Alzheimer's disease in the carriers of ApoE4 allele.[4]


GAB2 has been shown to interact with PTPN11,[1][5][6][7] PLCG2,[5] RICS,[8] Grb2,[1][6][9] PIK3R1,[6][7] CRKL,[7] AKT1[6] and SHC1.[5][6]


  1. 1.0 1.1 1.2 Zhao C, Yu DH, Shen R, Feng GS (Aug 1999). "Gab2, a new pleckstrin homology domain-containing adapter protein, acts to uncouple signaling from ERK kinase to Elk-1". J Biol Chem 274 (28): 19649–54. doi:10.1074/jbc.274.28.19649. PMID 10391903. 
  2. Nishida K, Yoshida Y, Itoh M, Fukada T, Ohtani T, Shirogane T, Atsumi T, Takahashi-Tezuka M, Ishihara K, Hibi M, Hirano T (Mar 1999). "Gab-family adapter proteins act downstream of cytokine and growth factor receptors and T- and B-cell antigen receptors". Blood 93 (6): 1809–16. PMID 10068651. 
  3. "Entrez Gene: GAB2 GRB2-associated binding protein 2". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9846. 
  4. Reiman EM, Webster JA, Myers AJ, Hardy J, Dunckley T, Zismann VL, Joshipura KD, Pearson JV, Hu-Lince D, Huentelman MJ, Craig DW, Coon KD, Liang WS, Herbert RH, Beach T, Rohrer KC, Zhao AS, Leung D, Bryden L, Marlowe L, Kaleem M, Mastroeni D, Grover A, Heward CB, Ravid R, Rogers J, Hutton ML, Melquist S, Petersen RC, Alexander GE, Caselli RJ, Kukull W, Papassotiropoulos A, Stephan DA (2007). "GAB2 Alleles Modify Alzheimer's Risk in APOE varepsilon4 Carriers". Neuron 54 (5): 713–720. doi:10.1016/j.neuron.2007.05.022. PMC 2587162. PMID 17553421.  Free full text Free PDF Genetic data in the public domain
  5. 5.0 5.1 5.2 Boudot, Cédric; Kadri Zahra, Petitfrère Emmanuelle, Lambert Elise, Chrétien Stany, Mayeux Patrick, Haye Bernard, Billat Claudine (Oct. 2002). "Phosphatidylinositol 3-kinase regulates glycosylphosphatidylinositol hydrolysis through PLC-gamma(2) activation in erythropoietin-stimulated cells". Cell. Signal. (England) 14 (10): 869–78. doi:10.1016/S0898-6568(02)00036-0. ISSN 0898-6568. PMID 12135708. 
  6. 6.0 6.1 6.2 6.3 6.4 Lynch, Danielle K; Daly Roger J (Jan. 2002). "PKB-mediated negative feedback tightly regulates mitogenic signalling via Gab2". EMBO J. (England) 21 (1–2): 72–82. doi:10.1093/emboj/21.1.72. ISSN 0261-4189. PMC 125816. PMID 11782427. 
  7. 7.0 7.1 7.2 Crouin, C; Arnaud M, Gesbert F, Camonis J, Bertoglio J (Apr. 2001). "A yeast two-hybrid study of human p97/Gab2 interactions with its SH2 domain-containing binding partners". FEBS Lett. (Netherlands) 495 (3): 148–53. doi:10.1016/S0014-5793(01)02373-0. ISSN 0014-5793. PMID 11334882. 
  8. Zhao, Chunmei; Ma Hong, Bossy-Wetzel Ella, Lipton Stuart A, Zhang Zhuohua, Feng Gen-Sheng (Sep. 2003). "GC-GAP, a Rho family GTPase-activating protein that interacts with signaling adapters Gab1 and Gab2". J. Biol. Chem. (United States) 278 (36): 34641–53. doi:10.1074/jbc.M304594200. ISSN 0021-9258. PMID 12819203. 
  9. Million, Ryan P; Harakawa Nari, Roumiantsev Sergei, Varticovski Lyuba, Van Etten Richard A (Jun. 2004). "A direct binding site for Grb2 contributes to transformation and leukemogenesis by the Tel-Abl (ETV6-Abl) tyrosine kinase". Mol. Cell. Biol. (United States) 24 (11): 4685–95. doi:10.1128/MCB.24.11.4685-4695.2004. ISSN 0270-7306. PMC 416425. PMID 15143164. 

Further reading

  • Hibi M, Hirano T (2000). "Gab-family adapter molecules in signal transduction of cytokine and growth factor receptors, and T and B cell antigen receptors". Leuk. Lymphoma 37 (3–4): 299–307. doi:10.3109/10428190009089430. PMID 10752981. 
  • Gold MR, Ingham RJ, McLeod SJ, et al. (2001). "Targets of B-cell antigen receptor signaling: the phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase-3 signaling pathway and the Rap1 GTPase". Immunol. Rev. 176: 47–68. doi:10.1034/j.1600-065X.2000.00601.x. PMID 11043767. 
  • Nagase T, Ishikawa K, Miyajima N, et al. (1998). "Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro". DNA Res. 5 (1): 31–9. doi:10.1093/dnares/5.1.31. PMID 9628581. 
  • Wickrema A, Uddin S, Sharma A, et al. (1999). "Engagement of Gab1 and Gab2 in erythropoietin signaling". J. Biol. Chem. 274 (35): 24469–74. doi:10.1074/jbc.274.35.24469. PMID 10455108. 
  • Bone H, Welham MJ (2000). "Shc associates with the IL-3 receptor beta subunit, SHIP and Gab2 following IL-3 stimulation. Contribution of Shc PTB and SH2 domains". Cell. Signal. 12 (3): 183–94. doi:10.1016/S0898-6568(99)00088-1. PMID 10704825. 
  • Liu Y, Jenkins B, Shin JL, Rohrschneider LR (2001). "Scaffolding protein Gab2 mediates differentiation signaling downstream of Fms receptor tyrosine kinase". Mol. Cell. Biol. 21 (9): 3047–56. doi:10.1128/MCB.21.9.3047-3056.2001. PMC 86933. PMID 11287610. 
  • Crouin C, Arnaud M, Gesbert F, et al. (2001). "A yeast two-hybrid study of human p97/Gab2 interactions with its SH2 domain-containing binding partners". FEBS Lett. 495 (3): 148–53. doi:10.1016/S0014-5793(01)02373-0. PMID 11334882. 
  • Bouscary D, Lecoq-Lafon C, Chrétien S, et al. (2001). "Role of Gab proteins in phosphatidylinositol 3-kinase activation by thrombopoietin (Tpo)". Oncogene 20 (18): 2197–204. doi:10.1038/sj.onc.1204317. PMID 11402314. 
  • Wu C, Lai CF, Mobley WC (2001). "Nerve growth factor activates persistent Rap1 signaling in endosomes". J. Neurosci. 21 (15): 5406–16. PMID 11466412. 
  • Yamasaki S, Nishida K, Hibi M, et al. (2002). "Docking protein Gab2 is phosphorylated by ZAP-70 and negatively regulates T cell receptor signaling by recruitment of inhibitory molecules". J. Biol. Chem. 276 (48): 45175–83. doi:10.1074/jbc.M105384200. PMID 11572860. 
  • Yamada K, Nishida K, Hibi M, et al. (2001). "Comparative FISH mapping of Gab1 and Gab2 genes in human, mouse and rat". Cytogenet. Cell Genet. 94 (1–2): 39–42. doi:10.1159/000048780. PMID 11701952. 
  • Lynch DK, Daly RJ (2002). "PKB-mediated negative feedback tightly regulates mitogenic signalling via Gab2". EMBO J. 21 (1–2): 72–82. doi:10.1093/emboj/21.1.72. PMC 125816. PMID 11782427. 
  • Wheadon H, Paling NR, Welham MJ (2002). "Molecular interactions of SHP1 and SHP2 in IL-3-signalling". Cell. Signal. 14 (3): 219–29. doi:10.1016/S0898-6568(01)00241-8. PMID 11812650. 
  • Dorsey JF, Cunnick JM, Mane SM, Wu J (2002). "Regulation of the Erk2-Elk1 signaling pathway and megakaryocytic differentiation of Bcr-Abl(+) K562 leukemic cells by Gab2". Blood 99 (4): 1388–97. doi:10.1182/blood.V99.4.1388. PMID 11830491. 
  • Hill RJ, Zozulya S, Lu YL, et al. (2002). "The lymphoid protein tyrosine phosphatase Lyp interacts with the adaptor molecule Grb2 and functions as a negative regulator of T-cell activation". Exp. Hematol. 30 (3): 237–44. doi:10.1016/S0301-472X(01)00794-9. PMID 11882361. 
  • Yu WM, Hawley TS, Hawley RG, Qu CK (2002). "Role of the docking protein Gab2 in beta(1)-integrin signaling pathway-mediated hematopoietic cell adhesion and migration". Blood 99 (7): 2351–9. doi:10.1182/blood.V99.7.2351. PMID 11895767. 
  • Mao Y, Lee AW (2005). "A novel role for Gab2 in bFGF-mediated cell survival during retinoic acid-induced neuronal differentiation". J. Cell Biol. 170 (2): 305–16. doi:10.1083/jcb.200505061. PMC 2171408. PMID 16009726. 

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