GAB1

GRB2-associated binding protein 1

Identifiers

External IDs

OMIM: 604439 MGI: 108088 HomoloGene: 1542 GeneCards: GAB1 Gene

Gene Ontology
Molecular function	• SH3/SH2 adaptor activity • protein binding
Cellular component	• cytosol • cytosol
Biological process	• epidermal growth factor receptor signaling pathway • cell proliferation • insulin receptor signaling pathway • fibroblast growth factor receptor signaling pathway
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 4:
144.26 – 144.4 Mb

Chr 8:
83.29 – 83.4 Mb

PubMed search

[1]

[2]

GRB2-associated-binding protein 1 is a protein that in humans is encoded by the GAB1 gene.^[1]

The protein encoded by this gene is a member of the IRS1-like multisubstrate docking protein family. The encoded protein is an important mediator of branching tubulogenesis and plays a central role in cellular growth response, transformation and apoptosis. Two transcript variants encoding different isoforms have been found for this gene.^[2]

Interactions

GAB1 has been shown to interact with Grb2,^[3]^[4]^[1] PIK3R1,^[5]^[1]^[6] PTPN11,^[7]^[6] CRKL,^[8] PLCG1^[9]^[1] and MAP3K3.^[10]

References

^ ^a ^b ^c ^d Holgado-Madruga M, Emlet DR, Moscatello DK, Godwin AK, Wong AJ (Apr 1996). "A Grb2-associated docking protein in EGF- and insulin-receptor signalling". Nature 379 (6565): 560–4. doi:10.1038/379560a0. PMID 8596638.
^ "Entrez Gene: GAB1 GRB2-associated binding protein 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=2549.
^ Oneyama, Chitose; Nakano Hirofumi, Sharma Sreenath V (Mar. 2002). "UCS15A, a novel small molecule, SH3 domain-mediated protein-protein interaction blocking drug". Oncogene (England) 21 (13): 2037–50. doi:10.1038/sj.onc.1205271. ISSN 0950-9232. PMID 11960376.
^ Lewitzky, M; Kardinal C, Gehring N H, Schmidt E K, Konkol B, Eulitz M, Birchmeier W, Schaeper U, Feller S M (Mar. 2001). "The C-terminal SH3 domain of the adapter protein Grb2 binds with high affinity to sequences in Gab1 and SLP-76 which lack the SH3-typical P-x-x-P core motif". Oncogene (England) 20 (9): 1052–62. doi:10.1038/sj.onc.1204202. ISSN 0950-9232. PMID 11314042.
^ Bertagnolo, V; Marchisio M, Volinia S, Caramelli E, Capitani S (Dec. 1998). "Nuclear association of tyrosine-phosphorylated Vav to phospholipase C-gamma1 and phosphoinositide 3-kinase during granulocytic differentiation of HL-60 cells". FEBS Lett. (NETHERLANDS) 441 (3): 480–4. doi:10.1016/S0014-5793(98)01593-2. ISSN 0014-5793. PMID 9891995.
^ ^a ^b Rocchi, S; Tartare-Deckert S, Murdaca J, Holgado-Madruga M, Wong A J, Van Obberghen E (Jul. 1998). "Determination of Gab1 (Grb2-associated binder-1) interaction with insulin receptor-signaling molecules". Mol. Endocrinol. (UNITED STATES) 12 (7): 914–23. doi:10.1210/me.12.7.914. ISSN 0888-8809. PMID 9658397.
^ Saito, Yuji; Hojo Yukihiro, Tanimoto Tatsuo, Abe Jun-ichi, Berk Bradford C (Jun. 2002). "Protein kinase C-alpha and protein kinase C-epsilon are required for Grb2-associated binder-1 tyrosine phosphorylation in response to platelet-derived growth factor". J. Biol. Chem. (United States) 277 (26): 23216–22. doi:10.1074/jbc.M200605200. ISSN 0021-9258. PMID 11940581.
^ Sakkab, D; Lewitzky M, Posern G, Schaeper U, Sachs M, Birchmeier W, Feller S M (Apr. 2000). "Signaling of hepatocyte growth factor/scatter factor (HGF) to the small GTPase Rap1 via the large docking protein Gab1 and the adapter protein CRKL". J. Biol. Chem. (UNITED STATES) 275 (15): 10772–8. doi:10.1074/jbc.275.15.10772. ISSN 0021-9258. PMID 10753869.
^ Ueno, E; Haruta T, Uno T, Usui I, Iwata M, Takano A, Kawahara J, Sasaoka T, Ishibashi O, Kobayashi M (Jul. 2001). "Potential role of Gab1 and phospholipase C-gamma in osmotic shock-induced glucose uptake in 3T3-L1 adipocytes". Horm. Metab. Res. (Germany) 33 (7): 402–6. doi:10.1055/s-2001-16227. ISSN 0018-5043. PMID 11507676.
^ Che, Wenyi; Lerner-Marmarosh Nicole, Huang Qunhua, Osawa Masaki, Ohta Shinsuke, Yoshizumi Masanori, Glassman Michael, Lee Jiing-Dwan, Yan Chen, Berk Bradford C, Abe Jun-Ichi (Jun. 2002). "Insulin-like growth factor-1 enhances inflammatory responses in endothelial cells: role of Gab1 and MEKK3 in TNF-alpha-induced c-Jun and NF-kappaB activation and adhesion molecule expression". Circ. Res. (United States) 90 (11): 1222–30. doi:10.1161/01.RES.0000021127.83364.7D. PMID 12065326.

Fixman ED, Holgado-Madruga M, Nguyen L et al. (1997). "Efficient cellular transformation by the Met oncoprotein requires a functional Grb2 binding site and correlates with phosphorylation of the Grb2-associated proteins, Cbl and Gab1". J. Biol. Chem. 272 (32): 20167–72. doi:10.1074/jbc.272.32.20167. PMID 9242692.
Nguyen L, Holgado-Madruga M, Maroun C et al. (1997). "Association of the multisubstrate docking protein Gab1 with the hepatocyte growth factor receptor requires a functional Grb2 binding site involving tyrosine 1356". J. Biol. Chem. 272 (33): 20811–9. doi:10.1074/jbc.272.33.20811. PMID 9252406.
Holgado-Madruga M, Moscatello DK, Emlet DR et al. (1997). "Grb2-associated binder-1 mediates phosphatidylinositol 3-kinase activation and the promotion of cell survival by nerve growth factor". Proc. Natl. Acad. Sci. U.S.A. 94 (23): 12419–24. doi:10.1073/pnas.94.23.12419. PMC 24976. PMID 9356464. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=24976.
Rocchi S, Tartare-Deckert S, Murdaca J et al. (1998). "Determination of Gab1 (Grb2-associated binder-1) interaction with insulin receptor-signaling molecules". Mol. Endocrinol. 12 (7): 914–23. doi:10.1210/me.12.7.914. PMID 9658397.
Qiu M, Hua S, Agrawal M et al. (1999). "Molecular cloning and expression of human grap-2, a novel leukocyte-specific SH2- and SH3-containing adaptor-like protein that binds to gab-1". Biochem. Biophys. Res. Commun. 253 (2): 443–7. doi:10.1006/bbrc.1998.9795. PMID 9878555.
Lehr S, Kotzka J, Herkner A et al. (1999). "Identification of tyrosine phosphorylation sites in human Gab-1 protein by EGF receptor kinase in vitro". Biochemistry 38 (1): 151–9. doi:10.1021/bi9818265. PMID 9890893.
Maroun CR, Holgado-Madruga M, Royal I et al. (1999). "The Gab1 PH domain is required for localization of Gab1 at sites of cell-cell contact and epithelial morphogenesis downstream from the met receptor tyrosine kinase". Mol. Cell. Biol. 19 (3): 1784–99. PMC 83972. PMID 10022866. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=83972.
Nishida K, Yoshida Y, Itoh M et al. (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.
Gual P, Giordano S, Williams TA et al. (2000). "Sustained recruitment of phospholipase C-gamma to Gab1 is required for HGF-induced branching tubulogenesis". Oncogene 19 (12): 1509–18. doi:10.1038/sj.onc.1203514. PMID 10734310.
Braun L, Ghebrehiwet B, Cossart P (2000). "gC1q-R/p32, a C1q-binding protein, is a receptor for the InlB invasion protein of Listeria monocytogenes". EMBO J. 19 (7): 1458–66. doi:10.1093/emboj/19.7.1458. PMC 310215. PMID 10747014. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=310215.
Sakkab D, Lewitzky M, Posern G et al. (2000). "Signaling of hepatocyte growth factor/scatter factor (HGF) to the small GTPase Rap1 via the large docking protein Gab1 and the adapter protein CRKL". J. Biol. Chem. 275 (15): 10772–8. doi:10.1074/jbc.275.15.10772. PMID 10753869.
Lehr S, Kotzka J, Herkner A et al. (2000). "Identification of major tyrosine phosphorylation sites in the human insulin receptor substrate Gab-1 by insulin receptor kinase in vitro". Biochemistry 39 (35): 10898–907. doi:10.1021/bi000982k. PMID 10978177.
Sachs M, Brohmann H, Zechner D et al. (2000). "Essential role of Gab1 for signaling by the c-Met receptor in vivo". J. Cell Biol. 150 (6): 1375–84. doi:10.1083/jcb.150.6.1375. PMC 2150711. PMID 10995442. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2150711.
Yart A, Laffargue M, Mayeux P et al. (2001). "A critical role for phosphoinositide 3-kinase upstream of Gab1 and SHP2 in the activation of ras and mitogen-activated protein kinases by epidermal growth factor". J. Biol. Chem. 276 (12): 8856–64. doi:10.1074/jbc.M006966200. PMID 11134009.
Ingham RJ, Santos L, Dang-Lawson M et al. (2001). "The Gab1 docking protein links the b cell antigen receptor to the phosphatidylinositol 3-kinase/Akt signaling pathway and to the SHP2 tyrosine phosphatase". J. Biol. Chem. 276 (15): 12257–65. doi:10.1074/jbc.M010590200. PMID 11278704.
Lewitzky M, Kardinal C, Gehring NH et al. (2001). "The C-terminal SH3 domain of the adapter protein Grb2 binds with high affinity to sequences in Gab1 and SLP-76 which lack the SH3-typical P-x-x-P core motif". Oncogene 20 (9): 1052–62. doi:10.1038/sj.onc.1204202. PMID 11314042.
Cunnick JM, Mei L, Doupnik CA, Wu J (2001). "Phosphotyrosines 627 and 659 of Gab1 constitute a bisphosphoryl tyrosine-based activation motif (BTAM) conferring binding and activation of SHP2". J. Biol. Chem. 276 (26): 24380–7. doi:10.1074/jbc.M010275200. PMID 11323411.
Kurokawa K, Iwashita T, Murakami H et al. (2001). "Identification of SNT/FRS2 docking site on RET receptor tyrosine kinase and its role for signal transduction". Oncogene 20 (16): 1929–38. doi:10.1038/sj.onc.1204290. PMID 11360177.
Kameda H, Risinger JI, Han BB et al. (2001). "Identification of epidermal growth factor receptor- Grb2-associated binder-1-SHP-2 complex formation and its functional loss during neoplastic cell progression". Cell Growth Differ. 12 (6): 307–18. PMID 11432805.

GAB1

Interactions

References

Further reading