GRB10

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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
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Wikidata
View/Edit Human

Growth factor receptor-bound protein 10 also known as insulin receptor-binding protein Grb-IR is a protein that in humans is encoded by the GRB10 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 insulin receptors and insulin-like growth-factor receptors (e.g., IGF1R and IGF2R). Overexpression of some isoforms of the encoded protein inhibits tyrosine kinase activity and results in growth suppression. This gene is imprinted in a highly isoform- and tissue-specific manner. Alternatively spliced transcript variants encoding different isoforms have been identified.

Animal studies

Mice whose paternally inherited Grb10 gene is inactivated are more aggressive while those whose maternally inherited allele is inactivated exhibit foetal overgrowth and are significantly bigger than wild-type litter-mates.

Interactions

GRB10 has been shown to interact with

• Abl gene,
• BCR gene,
• C-Raf,
• c-Kit,
• Insulin receptor,
• Insulin-like growth factor 1 receptor,
• MAP2K1, and
• RET proto-oncogene.

Further reading

• Ramírez-Dueñas ML, Medina C, Ocampo-Campos R, Rivera H (1992). "Severe Silver-Russell syndrome and translocation (17;20) (q25;q13)". Clin. Genet. 41 (1): 51–3. doi:10.1111/j.1399-0004.1992.tb03630.x. PMID 1633648.
• Liu F, Roth RA (1995). "Grb-IR: a SH2-domain-containing protein that binds to the insulin receptor and inhibits its function". Proc. Natl. Acad. Sci. U.S.A. 92 (22): 10287–91. Bibcode:1995PNAS...9210287L. doi:10.1073/pnas.92.22.10287. PMC 40781. PMID 7479769.
• Pandey A, Duan H, Di Fiore PP, Dixit VM (1995). "The Ret receptor protein tyrosine kinase associates with the SH2-containing adapter protein Grb10". J. Biol. Chem. 270 (37): 21461–3. doi:10.1074/jbc.270.37.21461. PMID 7665556.
• Midro AT, Debek K, Sawicka A, et al. (1993). "Second observation of Silver-Russel syndrome in a carrier of a reciprocal translocation with one breakpoint at site 17q25". Clin. Genet. 44 (1): 53–5. doi:10.1111/j.1399-0004.1993.tb03845.x. PMID 8403458.
• Hansen H, Svensson U, Zhu J, et al. (1996). "Interaction between the Grb10 SH2 domain and the insulin receptor carboxyl terminus". J. Biol. Chem. 271 (15): 8882–6. doi:10.1074/jbc.271.15.8882. PMID 8621530.
• Morrione A, Valentinis B, Li S, et al. (1996). "Grb10: A new substrate of the insulin-like growth factor I receptor". Cancer Res. 56 (14): 3165–7. PMID 8764099.
• O'Neill TJ, Rose DW, Pillay TS, et al. (1996). "Interaction of a GRB-IR splice variant (a human GRB10 homolog) with the insulin and insulin-like growth factor I receptors. Evidence for a role in mitogenic signaling". J. Biol. Chem. 271 (37): 22506–13. doi:10.1074/jbc.271.37.22506. PMID 8798417.
• Stein E, Cerretti DP, Daniel TO (1996). "Ligand activation of ELK receptor tyrosine kinase promotes its association with Grb10 and Grb2 in vascular endothelial cells". J. Biol. Chem. 271 (38): 23588–93. doi:10.1074/jbc.271.38.23588. PMID 8798570.
• Frantz JD, Giorgetti-Peraldi S, Ottinger EA, Shoelson SE (1997). "Human GRB-IRbeta/GRB10. Splice variants of an insulin and growth factor receptor-binding protein with PH and SH2 domains". J. Biol. Chem. 272 (5): 2659–67. doi:10.1074/jbc.272.5.2659. PMID 9006901.
• Nagase T, Seki N, Ishikawa K, et al. (1997). "Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain". DNA Res. 3 (5): 321–9, 341–54. doi:10.1093/dnares/3.5.321. PMID 9039502.
• He W, Rose DW, Olefsky JM, Gustafson TA (1998). "Grb10 interacts differentially with the insulin receptor, insulin-like growth factor I receptor, and epidermal growth factor receptor via the Grb10 Src homology 2 (SH2) domain and a second novel domain located between the pleckstrin homology and SH2 domains". J. Biol. Chem. 273 (12): 6860–7. doi:10.1074/jbc.273.12.6860. PMID 9506989.
• Nantel A, Mohammad-Ali K, Sherk J, et al. (1998). "Interaction of the Grb10 adapter protein with the Raf1 and MEK1 kinases". J. Biol. Chem. 273 (17): 10475–84. doi:10.1074/jbc.273.17.10475. PMID 9553107.
• Moutoussamy S, Renaudie F, Lago F, et al. (1998). "Grb10 identified as a potential regulator of growth hormone (GH) signaling by cloning of GH receptor target proteins". J. Biol. Chem. 273 (26): 15906–12. doi:10.1074/jbc.273.26.15906. PMID 9632636.
• Bai RY, Jahn T, Schrem S, et al. (1998). "The SH2-containing adapter protein GRB10 interacts with BCR-ABL". Oncogene. 17 (8): 941–8. doi:10.1038/sj.onc.1202024. PMID 9747873.
• Mano H, Ohya K, Miyazato A, et al. (1998). "Grb10/GrbIR as an in vivo substrate of Tec tyrosine kinase". Genes Cells. 3 (7): 431–41. doi:10.1046/j.1365-2443.1998.00201.x. PMID 9753425.
• "Toward a complete human genome sequence". Genome Res. 8 (11): 1097–108. 1999. doi:10.1101/gr.8.11.1097. PMID 9847074.
• Angrist M, Bolk S, Bentley K, et al. (1999). "Genomic structure of the gene for the SH2 and pleckstrin homology domain-containing protein GRB10 and evaluation of its role in Hirschsprung disease". Oncogene. 17 (23): 3065–70. doi:10.1038/sj.onc.1202226. PMID 9881709.
• Wang J, Dai H, Yousaf N, et al. (1999). "Grb10, a positive, stimulatory signaling adapter in platelet-derived growth factor BB-, insulin-like growth factor I-, and insulin-mediated mitogenesis". Mol. Cell. Biol. 19 (9): 6217–28. PMC 84567. PMID 10454568.

External links

• GRB10+Protein at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.