GRB7
Growth factor receptor-bound protein 7, also known as GRB7, is a protein that in humans is encoded by the GRB7 gene.[1][2]
Function
The product of this gene belongs to a small family of adaptor proteins that are known to interact with a number of receptor tyrosine kinases and signaling molecules. This gene encodes a growth factor receptor-binding protein that interacts with epidermal growth factor receptor (EGFR) and ephrin receptors. The protein plays a role in the integrin signaling pathway and cell migration by binding with focal adhesion kinase (FAK). Alternative splicing results in multiple transcript variants encoding different isoforms, although the full-length natures of only two of the variants have been determined to date.[1]
Clinical significance
GRB7 is an SH2-domain adaptor protein that binds to receptor tyrosine kinases and provides the intra-cellular direct link to the Ras proto-oncogene. Human GRB7 is located on the long arm of chromosome 17, next to the ERBB2 (alias HER2/neu) proto-oncogene.
These two genes are commonly co-amplified (present in excess copies) in breast cancers. GRB7 thought to be involved in migration , is well known to be over-expressed in testicular germ cell tumors, esophageal cancers, and gastric cancers.
Interactions
GRB7 has been shown to interact with Insulin receptor,[3] PTK2,[4] RET proto-oncogene,[5] Rnd1[6] and EPH receptor B1.[7]
References
- ↑ 1.0 1.1 "Entrez Gene: GRB7 growth factor receptor-bound protein 7".
- ↑ Tanaka S, Mori M, Akiyoshi T, Tanaka Y, Mafune K, Wands JR, Sugimachi K (August 1998). "A novel variant of human Grb7 is associated with invasive esophageal carcinoma". J. Clin. Invest. 102 (4): 821–7. doi:10.1172/JCI2921. PMC 508945. PMID 9710451.
- ↑ Kasus-Jacobi, A; Béréziat V; Perdereau D; Girard J; Burnol A F (April 2000). "Evidence for an interaction between the insulin receptor and Grb7. A role for two of its binding domains, PIR and SH2". Oncogene (ENGLAND) 19 (16): 2052–9. doi:10.1038/sj.onc.1203469. ISSN 0950-9232. PMID 10803466.
- ↑ Han, D C; Guan J L (August 1999). "Association of focal adhesion kinase with Grb7 and its role in cell migration". J. Biol. Chem. (UNITED STATES) 274 (34): 24425–30. doi:10.1074/jbc.274.34.24425. ISSN 0021-9258. PMID 10446223.
- ↑ Pandey, A; Liu X; Dixon J E; Di Fiore P P; Dixit V M (May 1996). "Direct association between the Ret receptor tyrosine kinase and the Src homology 2-containing adapter protein Grb7". J. Biol. Chem. (UNITED STATES) 271 (18): 10607–10. doi:10.1074/jbc.271.18.10607. ISSN 0021-9258. PMID 8631863.
- ↑ Vayssière, B; Zalcman G; Mahé Y; Mirey G; Ligensa T; Weidner K M; Chardin P; Camonis J (February 2000). "Interaction of the Grb7 adapter protein with Rnd1, a new member of the Rho family". FEBS Lett. (NETHERLANDS) 467 (1): 91–6. doi:10.1016/S0014-5793(99)01530-6. ISSN 0014-5793. PMID 10664463.
- ↑ Han, Dong Cho; Shen Tang-Long; Miao Hui; Wang Bingcheng; Guan Jun-Lin (November 2002). "EphB1 associates with Grb7 and regulates cell migration". J. Biol. Chem. (United States) 277 (47): 45655–61. doi:10.1074/jbc.M203165200. ISSN 0021-9258. PMID 12223469.
Further reading
- Han DC, Shen TL, Guan JL (2001). "The Grb7 family proteins: structure, interactions with other signaling molecules and potential cellular functions.". Oncogene 20 (44): 6315–21. doi:10.1038/sj.onc.1204775. PMID 11607834.
- Margolis B, Silvennoinen O, Comoglio F et al. (1992). "High-efficiency expression/cloning of epidermal growth factor-receptor-binding proteins with Src homology 2 domains.". Proc. Natl. Acad. Sci. U.S.A. 89 (19): 8894–8. doi:10.1073/pnas.89.19.8894. PMC 50030. PMID 1409582.
- Skotheim RI, Abeler VM, Nesland JM et al. (2003). "Candidate genes for testicular cancer evaluated by in situ protein expression analyses on tissue microarrays.". Neoplasia. 5 (5): 397–404. doi:10.1016/s1476-5586(03)80042-8. PMC 1502610. PMID 14670177.
- Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.". Gene 138 (1-2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Pandey A, Liu X, Dixon JE et al. (1996). "Direct association between the Ret receptor tyrosine kinase and the Src homology 2-containing adapter protein Grb7.". J. Biol. Chem. 271 (18): 10607–10. doi:10.1074/jbc.271.18.10607. PMID 8631863.
- Yokote K, Margolis B, Heldin CH, Claesson-Welsh L (1997). "Grb7 is a downstream signaling component of platelet-derived growth factor alpha- and beta-receptors.". J. Biol. Chem. 271 (48): 30942–9. doi:10.1074/jbc.271.48.30942. PMID 8940081.
- Tanaka S, Mori M, Akiyoshi T et al. (1997). "Coexpression of Grb7 with epidermal growth factor receptor or Her2/erbB2 in human advanced esophageal carcinoma.". Cancer Res. 57 (1): 28–31. PMID 8988034.
- Janes PW, Lackmann M, Church WB et al. (1997). "Structural determinants of the interaction between the erbB2 receptor and the Src homology 2 domain of Grb7.". J. Biol. Chem. 272 (13): 8490–7. doi:10.1074/jbc.272.13.8490. PMID 9079677.
- Kishi T, Sasaki H, Akiyama N et al. (1997). "Molecular cloning of human GRB-7 co-amplified with CAB1 and c-ERBB-2 in primary gastric cancer.". Biochem. Biophys. Res. Commun. 232 (1): 5–9. doi:10.1006/bbrc.1997.6218. PMID 9125150.
- Dong LQ, Du H, Porter SG et al. (1997). "Cloning, chromosome localization, expression, and characterization of an Src homology 2 and pleckstrin homology domain-containing insulin receptor binding protein hGrb10gamma.". J. Biol. Chem. 272 (46): 29104–12. doi:10.1074/jbc.272.46.29104. PMID 9360986.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library.". Gene 200 (1-2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- Fiddes RJ, Campbell DH, Janes PW et al. (1998). "Analysis of Grb7 recruitment by heregulin-activated erbB receptors reveals a novel target selectivity for erbB3.". J. Biol. Chem. 273 (13): 7717–24. doi:10.1074/jbc.273.13.7717. PMID 9516479.
- Tanaka S, Mori M, Akiyoshi T et al. (1998). "A novel variant of human Grb7 is associated with invasive esophageal carcinoma.". J. Clin. Invest. 102 (4): 821–7. doi:10.1172/JCI2921. PMC 508945. PMID 9710451.
- Thömmes K, Lennartsson J, Carlberg M, Rönnstrand L (1999). "Identification of Tyr-703 and Tyr-936 as the primary association sites for Grb2 and Grb7 in the c-Kit/stem cell factor receptor.". Biochem. J. 341 (1): 211–6. doi:10.1042/0264-6021:3410211. PMC 1220349. PMID 10377264.
- Han DC, Guan JL (1999). "Association of focal adhesion kinase with Grb7 and its role in cell migration.". J. Biol. Chem. 274 (34): 24425–30. doi:10.1074/jbc.274.34.24425. PMID 10446223.
- Jones N, Master Z, Jones J et al. (1999). "Identification of Tek/Tie2 binding partners. Binding to a multifunctional docking site mediates cell survival and migration.". J. Biol. Chem. 274 (43): 30896–905. doi:10.1074/jbc.274.43.30896. PMID 10521483.
- Vayssière B, Zalcman G, Mahé Y et al. (2000). "Interaction of the Grb7 adapter protein with Rnd1, a new member of the Rho family.". FEBS Lett. 467 (1): 91–6. doi:10.1016/S0014-5793(99)01530-6. PMID 10664463.
- Kasus-Jacobi A, Béréziat V, Perdereau D et al. (2000). "Evidence for an interaction between the insulin receptor and Grb7. A role for two of its binding domains, PIR and SH2.". Oncogene 19 (16): 2052–9. doi:10.1038/sj.onc.1203469. PMID 10803466.
- Han DC, Shen TL, Guan JL (2000). "Role of Grb7 targeting to focal contacts and its phosphorylation by focal adhesion kinase in regulation of cell migration.". J. Biol. Chem. 275 (37): 28911–7. doi:10.1074/jbc.M001997200. PMID 10893408.
- Lee H, Volonte D, Galbiati F et al. (2001). "Constitutive and growth factor-regulated phosphorylation of caveolin-1 occurs at the same site (Tyr-14) in vivo: identification of a c-Src/Cav-1/Grb7 signaling cassette.". Mol. Endocrinol. 14 (11): 1750–75. doi:10.1210/me.14.11.1750. PMID 11075810.
- Skotheim RI, Abeler VM, Nesland JM et al. (2003). "Candidate genes for testicular cancer evaluated by in situ protein expression analyses on tissue microarrays.". Neoplasia. 5 (5): 397–404. doi:10.1016/s1476-5586(03)80042-8. PMC 1502610. PMID 14670177.
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External links
- GRB7 Adaptor Protein at the US National Library of Medicine Medical Subject Headings (MeSH)
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