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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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"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" . The Journal of Biological Chemistry . 274 (43): 30896–905. doi :10.1074/jbc.274.43.30896 PMID 10521483 . Vayssière B, Zalcman G, Mahé Y, Mirey G, Ligensa T, Weidner KM, Chardin P, Camonis J (Feb 2000). "Interaction of the Grb7 adapter protein with Rnd1, a new member of the Rho family" . FEBS Letters . 467 (1): 91–6. doi :10.1016/S0014-5793(99)01530-6 PMID 10664463 . S2CID 4901644 . 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, Shen TL, Guan JL (Sep 2000). "Role of Grb7 targeting to focal contacts and its phosphorylation by focal adhesion kinase in regulation of cell migration" . The Journal of Biological Chemistry . 275 (37): 28911–7. doi :10.1074/jbc.M001997200 PMID 10893408 . 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" . 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