Biology:GRB7

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

Growth factor receptor-bound protein 7, also known as GRB7, is a protein that in humans is encoded by the GRB7 gene.

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.

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:

• EPH receptor B1,
• Insulin receptor,
• PTK2,
• RET proto-oncogene, and
• Rnd1

Further reading

• "The Grb7 family proteins: structure, interactions with other signaling molecules and potential cellular functions". Oncogene 20 (44): 6315–21. Oct 2001. doi:10.1038/sj.onc.1204775. PMID 11607834. 
• "High-efficiency expression/cloning of epidermal growth factor-receptor-binding proteins with Src homology 2 domains". Proceedings of the National Academy of Sciences of the United States of America 89 (19): 8894–8. Oct 1992. doi:10.1073/pnas.89.19.8894. PMID 1409582. Bibcode: 1992PNAS...89.8894M. 
• "Candidate genes for testicular cancer evaluated by in situ protein expression analyses on tissue microarrays". Neoplasia 5 (5): 397–404. 2003. doi:10.1016/s1476-5586(03)80042-8. PMID 14670177. 
• "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. Jan 1994. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. 
• "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. May 1996. doi:10.1074/jbc.271.18.10607. PMID 8631863. 
• "Grb7 is a downstream signaling component of platelet-derived growth factor alpha- and beta-receptors". The Journal of Biological Chemistry 271 (48): 30942–9. Nov 1996. doi:10.1074/jbc.271.48.30942. PMID 8940081. 
• "Coexpression of Grb7 with epidermal growth factor receptor or Her2/erbB2 in human advanced esophageal carcinoma". Cancer Research 57 (1): 28–31. Jan 1997. PMID 8988034. 
• "Structural determinants of the interaction between the erbB2 receptor and the Src homology 2 domain of Grb7". The Journal of Biological Chemistry 272 (13): 8490–7. Mar 1997. doi:10.1074/jbc.272.13.8490. PMID 9079677. 
• "Molecular cloning of human GRB-7 co-amplified with CAB1 and c-ERBB-2 in primary gastric cancer". Biochemical and Biophysical Research Communications 232 (1): 5–9. Mar 1997. doi:10.1006/bbrc.1997.6218. PMID 9125150. 
• "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. Nov 1997. doi:10.1074/jbc.272.46.29104. PMID 9360986. 
• "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. Oct 1997. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. 
• "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. Mar 1998. doi:10.1074/jbc.273.13.7717. PMID 9516479. 
• "A novel variant of human Grb7 is associated with invasive esophageal carcinoma". The Journal of Clinical Investigation 102 (4): 821–7. Aug 1998. doi:10.1172/JCI2921. PMID 9710451. 
• "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. Jul 1999. doi:10.1042/0264-6021:3410211. PMID 10377264. 
• "Association of focal adhesion kinase with Grb7 and its role in cell migration". The Journal of Biological Chemistry 274 (34): 24425–30. Aug 1999. doi:10.1074/jbc.274.34.24425. PMID 10446223. 
• "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. Oct 1999. doi:10.1074/jbc.274.43.30896. PMID 10521483. 
• "Interaction of the Grb7 adapter protein with Rnd1, a new member of the Rho family". FEBS Letters 467 (1): 91–6. Feb 2000. doi:10.1016/S0014-5793(99)01530-6. PMID 10664463. 
• "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. Apr 2000. doi:10.1038/sj.onc.1203469. PMID 10803466. 
• "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. Sep 2000. doi:10.1074/jbc.M001997200. PMID 10893408. 
• "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. Nov 2000. doi:10.1210/mend.14.11.0553. PMID 11075810. 
• "Candidate genes for testicular cancer evaluated by in situ protein expression analyses on tissue microarrays". Neoplasia 5 (5): 397–404. 2003. doi:10.1016/s1476-5586(03)80042-8. PMID 14670177. 

External links

• GRB7+Adaptor+Protein at the US National Library of Medicine Medical Subject Headings (MeSH)