Scientific background: |
IGF1R(Insulin-like Growth Factor 1 (IGF-1) Receptor) is a protein found on the surface of human cells. It is a transmembrane receptor that is activated by a hormone called Insulin-like growth factor 1 (IGF-1) and by a related hormone called IGF-2. It belongs to the large class of tyrosine kinase receptors. The IGF1R gene is mapped on 15q26.3. IGF-1 plays an important role in growth and continues to have anabolic effects in adults - meaning that it can induce hypertrophy of skeletal muscle and other target tissues. Using a yeast 2-hybrid system, Dey et al. (1998) identified a regulatory subunit of phosphatidylinositol (PI) 3-kinase, PIK3R3, as a binding partner of IGF1R. Functional interaction between BRCA1 and SP1 in the regulation of the IGF1R gene was studied in Schneider cells, a Drosophila cell line which lacks endogenous SP1. In these cells, BRCA1 suppressed 45% of the SP1-induced trans-activation of the IGF1R promoter. Overexpression of the Grb10-binding fragment of Gigyf1 resulted in a significant increase in Igf1-stimulated Igf1r tyrosine phosphorylation. Like the insulin receptor, the IGF-1 receptor is a receptor tyrosine kinase - meaning it signals by causing the addition of a phosphate molecule on particular tyrosines. IGF-1 activates the Insulin receptor at approximately 0.1x the potency of insulin. Part of this signaling may be via IGF1R-InsulinReceptor heterodimers. |
References: |
1.Abbott, A. M., Bueno, R., Pedrini, M. T., Murray, J. M., Smith, R. J. Insulin-like growth factor I receptor gene structure. J. Biol. Chem. 267: 10759-10763, 1992.
2.Dey, B. R., Furlanetto, R. W., Nissley, S. P. Cloning of human p55-gamma, a regulatory subunit of phosphatidylinositol 3-kinase, by a yeast two-hybrid library screen with the insulin-like growth factor-I receptor. Gene 209: 175-183, 1998.
3.Giovannone, B., Lee, E., Laviola, L., Giorgino, F., Cleveland, K. A., Smith, R. J. Two novel proteins that are linked to insulin-like growth factor (IFG-I) receptors by the Grb10 adapter and modulate IGF-I signaling. J. Biol. Chem. 278: 31564-31573, 2003.
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