Protein-coding gene in the species Homo sapiens
Growth factor receptor-bound protein 7 , also known as GRB7 , is a protein that in humans is encoded by the GRB7 gene .[ 5] [ 6]
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.[ 5]
Clinical significance [ edit ] 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,[ 5] germ cell tumors , esophageal cancers , and gastric cancers .
GRB7 has been shown to interact with:
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The Journal of Biological Chemistry . 277 (47): 45655–61. doi :10.1074/jbc.M203165200 PMID 12223469 . ^ Kasus-Jacobi A, Béréziat V, Perdereau D, Girard J, Burnol AF (Apr 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, Guan JL (Aug 1999). "Association of focal adhesion kinase with Grb7 and its role in cell migration" . The Journal of Biological Chemistry . 274 (34): 24425–30. doi :10.1074/jbc.274.34.24425 PMID 10446223 . ^ Pandey A, Liu X, Dixon JE, Di Fiore PP, Dixit VM (May 1996). "Direct association between the Ret receptor tyrosine kinase and the Src homology 2-containing adapter protein Grb7" . The Journal of Biological Chemistry . 271 (18): 10607–10. doi :10.1074/jbc.271.18.10607 PMID 8631863 . ^ Vayssière B, Zalcman G, Mahé Y, Mirey G, Ligensa T, Weidner KM, Chardin P, Camonis J (Feb 2000). 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"Cloning, chromosome localization, expression, and characterization of an Src homology 2 and pleckstrin homology domain-containing insulin receptor binding protein hGrb10gamma" . The Journal of Biological Chemistry . 272 (46): 29104–12. doi :10.1074/jbc.272.46.29104 PMID 9360986 . Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 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, Sivertsen SP, Sasaki H, Wallasch C, Daly RJ (Mar 1998). "Analysis of Grb7 recruitment by heregulin-activated erbB receptors reveals a novel target selectivity for erbB3" . The Journal of Biological Chemistry . 273 (13): 7717–24. doi :10.1074/jbc.273.13.7717 PMID 9516479 . Tanaka S, Mori M, Akiyoshi T, Tanaka Y, Mafune K, Wands JR, Sugimachi K (Aug 1998). "A novel variant of human Grb7 is associated with invasive esophageal carcinoma" . The Journal of Clinical Investigation . 102 (4): 821–7. doi :10.1172/JCI2921 . PMC 508945 PMID 9710451 . Thömmes K, Lennartsson J, Carlberg M, Rönnstrand L (Jul 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" . The Biochemical Journal . 341 (1): 211–6. doi :10.1042/0264-6021:3410211 . PMC 1220349 PMID 10377264 . Han DC, Guan JL (Aug 1999). "Association of focal adhesion kinase with Grb7 and its role in cell migration" . The Journal of Biological Chemistry . 274 (34): 24425–30. doi :10.1074/jbc.274.34.24425 PMID 10446223 . Jones N, Master Z, Jones J, Bouchard D, Gunji Y, Sasaki H, Daly R, Alitalo K, Dumont DJ (Oct 1999). "Identification of Tek/Tie2 binding partners. Binding to a multifunctional docking site mediates cell survival and migration" . 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Lee H, Volonte D, Galbiati F, Iyengar P, Lublin DM, Bregman DB, Wilson MT, Campos-Gonzalez R, Bouzahzah B, Pestell RG, Scherer PE, Lisanti MP (Nov 2000). "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" . Molecular Endocrinology . 14 (11): 1750–75. doi :10.1210/mend.14.11.0553 PMID 11075810 . Skotheim RI, Abeler VM, Nesland JM, Fosså SD, Holm R, Wagner U, Flørenes VA, Aass N, Kallioniemi OP, Lothe RA (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 .
