GRB7

VALUE_ERROR (nil)
Identifiers
Aliases
External IDs	GeneCards: [1]
Orthologs
Species	Human	Mouse
Entrez	n/a	n/a
Ensembl	n/a	n/a
UniProt	n/a	n/a
RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
Location (UCSC)	n/a	n/a
PubMed search	n/a	n/a
Wikidata
View/Edit Human

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

Model organisms

Model organisms have been used in the study of GRB7 function. A conditional knockout mouse line called Grb7^{tm1b(EUCOMM)Wtsi} was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed: - In-depth immunological phenotyping

Grb7 knockout mouse phenotype

Characteristic	Phenotype
All data available at.
Peripheral blood leukocytes 6 Weeks	Normal
Haematology 6 Weeks	Normal
Homozygous viability at P14	Normal
Homozygous Fertility	Normal
Body weight	Normal
Neurological assessment	Normal
Grip strength	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology 16 Weeks	Normal
Peripheral blood leukocytes 16 Weeks	Normal
Heart weight	Normal
Salmonella infection	Normal
Cytotoxic T Cell Function	Normal
Spleen Immunophenotyping	Normal
Mesenteric Lymph Node Immunophenotyping	Normal
Bone Marrow Immunophenotyping	Normal
Epidermal Immune Composition	Normal
Trichuris Challenge	Normal

Further reading

• Han DC, Shen TL, Guan JL (Oct 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, Roonprapunt C, Skolnik E, Ullrich A, Schlessinger J (Oct 1992). "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. doi:10.1073/pnas.89.19.8894. PMC 50030. PMID 1409582.
• 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.
• Maruyama K, Sugano S (Jan 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, 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.
• Yokote K, Margolis B, Heldin CH, Claesson-Welsh L (Nov 1996). "Grb7 is a downstream signaling component of platelet-derived growth factor alpha- and beta-receptors". The Journal of Biological Chemistry. 271 (48): 30942–9. doi:10.1074/jbc.271.48.30942. PMID 8940081.
• Tanaka S, Mori M, Akiyoshi T, Tanaka Y, Mafune K, Wands JR, Sugimachi K (Jan 1997). "Coexpression of Grb7 with epidermal growth factor receptor or Her2/erbB2 in human advanced esophageal carcinoma". Cancer Research. 57 (1): 28–31. PMID 8988034.
• Janes PW, Lackmann M, Church WB, Sanderson GM, Sutherland RL, Daly RJ (Mar 1997). "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. doi:10.1074/jbc.272.13.8490. PMID 9079677.
• Kishi T, Sasaki H, Akiyama N, Ishizuka T, Sakamoto H, Aizawa S, Sugimura T, Terada M (Mar 1997). "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. doi:10.1006/bbrc.1997.6218. PMID 9125150.
• Dong LQ, Du H, Porter SG, Kolakowski LF, Lee AV, Mandarino LJ, Fan J, Yee D, Liu F, Mandarino J (Nov 1997). "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". 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.
• 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". Molecular Endocrinology. 14 (11): 1750–75. doi:10.1210/me.14.11.1750. 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.

External links

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