GRB7

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.

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.

GRB7 has been shown to interact with:

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• EPH receptor B1,{{cite journal | vauthors = Han DC, Shen TL, Miao H, Wang B, Guan JL | title = EphB1 associates with Grb7 and regulates cell migration | journal = The Journal of Biological Chemistry | volume = 277 | issue = 47 | pages = 45655–61 | date = Nov 2002 | pmid = 12223469 | doi = 10.1074/jbc.M203165200 | doi-access = free }}
• Insulin receptor,{{cite journal | vauthors = Kasus-Jacobi A, Béréziat V, Perdereau D, Girard J, Burnol AF | title = Evidence for an interaction between the insulin receptor and Grb7. A role for two of its binding domains, PIR and SH2 | journal = Oncogene | volume = 19 | issue = 16 | pages = 2052–9 | date = Apr 2000 | pmid = 10803466 | doi = 10.1038/sj.onc.1203469 | doi-access = free }}
• PTK2,{{cite journal | vauthors = Han DC, Guan JL | title = Association of focal adhesion kinase with Grb7 and its role in cell migration | journal = The Journal of Biological Chemistry | volume = 274 | issue = 34 | pages = 24425–30 | date = Aug 1999 | pmid = 10446223 | doi = 10.1074/jbc.274.34.24425| doi-access = free }}
• RET proto-oncogene,{{cite journal | vauthors = Pandey A, Liu X, Dixon JE, Di Fiore PP, Dixit VM | title = Direct association between the Ret receptor tyrosine kinase and the Src homology 2-containing adapter protein Grb7 | journal = The Journal of Biological Chemistry | volume = 271 | issue = 18 | pages = 10607–10 | date = May 1996 | pmid = 8631863 | doi = 10.1074/jbc.271.18.10607| doi-access = free }} and
• Rnd1{{cite journal | vauthors = Vayssière B, Zalcman G, Mahé Y, Mirey G, Ligensa T, Weidner KM, Chardin P, Camonis J | title = Interaction of the Grb7 adapter protein with Rnd1, a new member of the Rho family | journal = FEBS Letters | volume = 467 | issue = 1 | pages = 91–6 | date = Feb 2000 | pmid = 10664463 | doi = 10.1016/s0014-5793(99)01530-6| s2cid = 4901644 | doi-access = free }}

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{{reflist|33em}}

{{refbegin|33em}}

• {{cite journal | vauthors = Han DC, Shen TL, Guan JL | title = The Grb7 family proteins: structure, interactions with other signaling molecules and potential cellular functions | journal = Oncogene | volume = 20 | issue = 44 | pages = 6315–21 | date = Oct 2001 | pmid = 11607834 | doi = 10.1038/sj.onc.1204775 | doi-access = free }}
• {{cite journal | vauthors = Margolis B, Silvennoinen O, Comoglio F, Roonprapunt C, Skolnik E, Ullrich A, Schlessinger J | title = High-efficiency expression/cloning of epidermal growth factor-receptor-binding proteins with Src homology 2 domains | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 89 | issue = 19 | pages = 8894–8 | date = Oct 1992 | pmid = 1409582 | pmc = 50030 | doi = 10.1073/pnas.89.19.8894 | bibcode = 1992PNAS...89.8894M | doi-access = free }}
• {{cite journal | vauthors = Skotheim RI, Abeler VM, Nesland JM, Fosså SD, Holm R, Wagner U, Flørenes VA, Aass N, Kallioniemi OP, Lothe RA | title = Candidate genes for testicular cancer evaluated by in situ protein expression analyses on tissue microarrays | journal = Neoplasia | volume = 5 | issue = 5 | pages = 397–404 | year = 2003 | pmid = 14670177 | pmc = 1502610 | doi = 10.1016/s1476-5586(03)80042-8 }}
• {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–4 | date = Jan 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
• {{cite journal | vauthors = Pandey A, Liu X, Dixon JE, Di Fiore PP, Dixit VM | title = Direct association between the Ret receptor tyrosine kinase and the Src homology 2-containing adapter protein Grb7 | journal = The Journal of Biological Chemistry | volume = 271 | issue = 18 | pages = 10607–10 | date = May 1996 | pmid = 8631863 | doi = 10.1074/jbc.271.18.10607 | doi-access = free }}
• {{cite journal | vauthors = Yokote K, Margolis B, Heldin CH, Claesson-Welsh L | title = Grb7 is a downstream signaling component of platelet-derived growth factor alpha- and beta-receptors | journal = The Journal of Biological Chemistry | volume = 271 | issue = 48 | pages = 30942–9 | date = Nov 1996 | pmid = 8940081 | doi = 10.1074/jbc.271.48.30942 | doi-access = free }}
• {{cite journal | vauthors = Tanaka S, Mori M, Akiyoshi T, Tanaka Y, Mafune K, Wands JR, Sugimachi K | title = Coexpression of Grb7 with epidermal growth factor receptor or Her2/erbB2 in human advanced esophageal carcinoma | journal = Cancer Research | volume = 57 | issue = 1 | pages = 28–31 | date = Jan 1997 | pmid = 8988034 }}
• {{cite journal | vauthors = Janes PW, Lackmann M, Church WB, Sanderson GM, Sutherland RL, Daly RJ | title = Structural determinants of the interaction between the erbB2 receptor and the Src homology 2 domain of Grb7 | journal = The Journal of Biological Chemistry | volume = 272 | issue = 13 | pages = 8490–7 | date = Mar 1997 | pmid = 9079677 | doi = 10.1074/jbc.272.13.8490 | doi-access = free }}
• {{cite journal | vauthors = Kishi T, Sasaki H, Akiyama N, Ishizuka T, Sakamoto H, Aizawa S, Sugimura T, Terada M | title = Molecular cloning of human GRB-7 co-amplified with CAB1 and c-ERBB-2 in primary gastric cancer | journal = Biochemical and Biophysical Research Communications | volume = 232 | issue = 1 | pages = 5–9 | date = Mar 1997 | pmid = 9125150 | doi = 10.1006/bbrc.1997.6218 }}
• {{cite journal | vauthors = Dong LQ, Du H, Porter SG, Kolakowski LF, Lee AV, Mandarino LJ, Fan J, Yee D, Liu F, Mandarino J | title = Cloning, chromosome localization, expression, and characterization of an Src homology 2 and pleckstrin homology domain-containing insulin receptor binding protein hGrb10gamma | journal = The Journal of Biological Chemistry | volume = 272 | issue = 46 | pages = 29104–12 | date = Nov 1997 | pmid = 9360986 | doi = 10.1074/jbc.272.46.29104 | doi-access = free }}
• {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–56 | date = Oct 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
• {{cite journal | vauthors = Fiddes RJ, Campbell DH, Janes PW, Sivertsen SP, Sasaki H, Wallasch C, Daly RJ | title = Analysis of Grb7 recruitment by heregulin-activated erbB receptors reveals a novel target selectivity for erbB3 | journal = The Journal of Biological Chemistry | volume = 273 | issue = 13 | pages = 7717–24 | date = Mar 1998 | pmid = 9516479 | doi = 10.1074/jbc.273.13.7717 | doi-access = free }}
• {{cite journal | vauthors = Tanaka S, Mori M, Akiyoshi T, Tanaka Y, Mafune K, Wands JR, Sugimachi K | title = A novel variant of human Grb7 is associated with invasive esophageal carcinoma | journal = The Journal of Clinical Investigation | volume = 102 | issue = 4 | pages = 821–7 | date = Aug 1998 | pmid = 9710451 | pmc = 508945 | doi = 10.1172/JCI2921 }}
• {{cite journal | vauthors = Thömmes K, Lennartsson J, Carlberg M, Rönnstrand L | title = Identification of Tyr-703 and Tyr-936 as the primary association sites for Grb2 and Grb7 in the c-Kit/stem cell factor receptor | journal = The Biochemical Journal | volume = 341 | issue = 1 | pages = 211–6 | date = Jul 1999 | pmid = 10377264 | pmc = 1220349 | doi = 10.1042/0264-6021:3410211 }}
• {{cite journal | vauthors = Han DC, Guan JL | title = Association of focal adhesion kinase with Grb7 and its role in cell migration | journal = The Journal of Biological Chemistry | volume = 274 | issue = 34 | pages = 24425–30 | date = Aug 1999 | pmid = 10446223 | doi = 10.1074/jbc.274.34.24425 | doi-access = free }}
• {{cite journal | vauthors = Jones N, Master Z, Jones J, Bouchard D, Gunji Y, Sasaki H, Daly R, Alitalo K, Dumont DJ | title = Identification of Tek/Tie2 binding partners. Binding to a multifunctional docking site mediates cell survival and migration | journal = The Journal of Biological Chemistry | volume = 274 | issue = 43 | pages = 30896–905 | date = Oct 1999 | pmid = 10521483 | doi = 10.1074/jbc.274.43.30896 | doi-access = free }}
• {{cite journal | vauthors = Vayssière B, Zalcman G, Mahé Y, Mirey G, Ligensa T, Weidner KM, Chardin P, Camonis J | title = Interaction of the Grb7 adapter protein with Rnd1, a new member of the Rho family | journal = FEBS Letters | volume = 467 | issue = 1 | pages = 91–6 | date = Feb 2000 | pmid = 10664463 | doi = 10.1016/S0014-5793(99)01530-6 | s2cid = 4901644 | doi-access = free }}
• {{cite journal | vauthors = Kasus-Jacobi A, Béréziat V, Perdereau D, Girard J, Burnol AF | title = Evidence for an interaction between the insulin receptor and Grb7. A role for two of its binding domains, PIR and SH2 | journal = Oncogene | volume = 19 | issue = 16 | pages = 2052–9 | date = Apr 2000 | pmid = 10803466 | doi = 10.1038/sj.onc.1203469 | doi-access = free }}
• {{cite journal | vauthors = Han DC, Shen TL, Guan JL | title = Role of Grb7 targeting to focal contacts and its phosphorylation by focal adhesion kinase in regulation of cell migration | journal = The Journal of Biological Chemistry | volume = 275 | issue = 37 | pages = 28911–7 | date = Sep 2000 | pmid = 10893408 | doi = 10.1074/jbc.M001997200 | doi-access = free }}
• {{cite journal | vauthors = 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 | title = 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 | journal = Molecular Endocrinology | volume = 14 | issue = 11 | pages = 1750–75 | date = Nov 2000 | pmid = 11075810 | doi = 10.1210/mend.14.11.0553 | doi-access = free }}
• {{cite journal | vauthors = Skotheim RI, Abeler VM, Nesland JM, Fosså SD, Holm R, Wagner U, Flørenes VA, Aass N, Kallioniemi OP, Lothe RA | title = Candidate genes for testicular cancer evaluated by in situ protein expression analyses on tissue microarrays | journal = Neoplasia | volume = 5 | issue = 5 | pages = 397–404 | year = 2003 | pmid = 14670177 | pmc = 1502610 | doi = 10.1016/s1476-5586(03)80042-8 }}

{{refend}}

• {{MeshName|GRB7+Adaptor+Protein}}

{{PDB Gallery|geneid=2886}}

{{Adaptor proteins}}

Category:Proteins