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Gene Review

IGF1R  -  insulin-like growth factor 1 receptor

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Disease relevance of IGF1R


High impact information on IGF1R

  • When quiescent cultures of bovine fibroblasts were stimulated with 10 nM IGF-I and total cell lysates immunoblotted with anti-phosphotyrosine antibody, we observed a band at approximately 97 kDa, representing the beta-subunit of the IGF-I receptor, and a predominant tyrosyl-phosphorylated species migrating as a broad band between 170 and 190 kDa [5].
  • These studies suggest that insulin, via interaction with insulin receptors on bovine fibroblasts, regulates IGF-I action at a step distal to IGF-I receptor binding and are consistent with desensitization occurring at an intracellular step in the mitogenic pathway shared by insulin and IGF-I [6].
  • In the present study, we use this model system to determine insulin and IGF-I receptor interplay in the regulation of proto-oncogenes involved in mitogenesis [7].
  • These findings demonstrate a cascade of insulin and IGF-I receptor tyrosine kinase-mediated pathways in the bovine luteal cell, manifested as increased activity of signal transduction enzymes and increased DNA synthesis [8].
  • The potential role of insulin and IGF-I receptor tyrosine kinases in the bovine luteal cell was investigated in terms of autophosphorylation of the receptor and phosphorylation of endogenous and exogenous substrates [8].

Biological context of IGF1R


Anatomical context of IGF1R


Associations of IGF1R with chemical compounds

  • Data from crosslinking experiments with and without neuraminidase treatment indicate that the binding subunits of the retinal IGF-I receptor exist in two subpopulations (Mr = 121- and 131 kDa), and that the larger of the two subunits has either a greater number or more exposed sialic acid residues [16].
  • IGF-I significantly increased thymidine incorporation, and its effect was completely inhibited by IGF-I receptor antibody [17].
  • Taken together, our results indicate not only the presence of both IGF-I and IGF-II/Man6P receptors on BAM, but also provide evidence of the linkage of the IGF-I receptor to the inositol phosphate system [18].

Regulatory relationships of IGF1R

  • IGF-I and IGF-II stimulated tyrosine kinase activity and autophosphorylation of the IGF-I receptor beta-subunit (Mr approximately 94,000) with equal potency (ED50 approximately 1 nM), whereas insulin was approximately 5 times less potent [19].

Other interactions of IGF1R


Analytical, diagnostic and therapeutic context of IGF1R


  1. Antiproliferative and apoptotic effect of ascorbyl stearate in human glioblastoma multiforme cells: modulation of insulin-like growth factor-I receptor (IGF-IR) expression. Naidu, K.A., Tang, J.L., Naidu, K.A., Prockop, L.D., Nicosia, S.V., Coppola, D. J. Neurooncol. (2001) [Pubmed]
  2. Effects of estriol on proliferative activity and expression of insulin-like growth factor-I (IGF-I) and IGF-I receptor mRNA in cultured human osteoblast-like osteosarcoma cells. Mochizuki, S., Yoshida, S., Yamanaka, Y., Matsuo, H., Maruo, T. Gynecol. Endocrinol. (2005) [Pubmed]
  3. Prions in control of cell glycosylation. Hounsell, E.F. Biochem. J. (2004) [Pubmed]
  4. Decreased insulin-like growth factor-I (IGF-I) receptor sites on circulating mononuclear cells from cows with persistent lymphocytosis. Zhao, X., McBride, B.W., Trouten-Radford, L., Lissemore, K. J. Recept. Res. (1993) [Pubmed]
  5. Insulin and interleukin-4 induce desensitization to the mitogenic effects of insulin-like growth factor-I. Pivotal role for insulin receptor substrate-2. Haddad, T.C., Conover, C.A. J. Biol. Chem. (1997) [Pubmed]
  6. Physiological concentrations of insulin induce cellular desensitization to the mitogenic effects of insulin-like growth factor I. Conover, C.A., Clarkson, J.T., Bale, L.K. Diabetes (1994) [Pubmed]
  7. Insulin-like growth factor I induction of c-myc expression in bovine fibroblasts can be blocked by antecedent insulin receptor activation. Conover, C.A., Bale, L.K. Exp. Cell Res. (1998) [Pubmed]
  8. Characterization of insulin and insulin-like growth factor-I actions in the bovine luteal cell: regulation of receptor tyrosine kinase activity, phosphatidylinositol-3-kinase, and deoxyribonucleic acid synthesis. Chakravorty, A., Joslyn, M.I., Davis, J.S. Endocrinology (1993) [Pubmed]
  9. Stimulation of the development of bovine embryos by insulin and insulin-like growth factor-I (IGF-I) is mediated through the IGF-I receptor. Matsui, M., Takahashi, Y., Hishinuma, M., Kanagawa, H. Theriogenology (1997) [Pubmed]
  10. Stimulation of DNA synthesis and c-fos expression in corneal endothelium by insulin or insulin-like growth factor-I. Feldman, S.T., Gately, D., Seely, B.L., Schonthal, A., Feramisco, J.R. Invest. Ophthalmol. Vis. Sci. (1993) [Pubmed]
  11. Ethanol inhibits insulin-like growth factor-1-mediated signalling and proliferation of C6 rat glioblastoma cells. Resnicoff, M., Rubini, M., Baserga, R., Rubin, R. Lab. Invest. (1994) [Pubmed]
  12. Identification and characterization of insulin-like growth factor I (IGF-I) and IGF-II/mannose-6-phosphate (IGF-II/M6P) receptors in bovine adrenal cells. Weber, M.M., Kiess, W., Beikler, T., Simmler, P., Reichel, M., Adelmann, B., Kessler, U., Engelhardt, D. Eur. J. Endocrinol. (1994) [Pubmed]
  13. Receptor binding and growth-promoting activity of insulin-like growth factor-I in a bovine mammary epithelial cell line (MAC-T3). Zhao, X., McBride, B.W., Politis, I., Huynh, H.T., Akers, R.M., Burton, J.H., Turner, J.D. J. Endocrinol. (1992) [Pubmed]
  14. Autocrine/paracrine mechanism of insulin-like growth factor-1 secretion, and the effect of insulin-like growth factor-1 on proteoglycan synthesis in bovine intervertebral discs. Osada, R., Ohshima, H., Ishihara, H., Yudoh, K., Sakai, K., Matsui, H., Tsuji, H. J. Orthop. Res. (1996) [Pubmed]
  15. Phosphotyrosine-containing proteins in bovine chromaffin cells: effects of insulin-like growth factor I (IGF-I). Cahill, A.L., Perlman, R.L. Cell. Mol. Neurobiol. (1991) [Pubmed]
  16. IGF-I receptors in the bovine neural retina: structure, kinase activity and comparison with retinal insulin receptors. Waldbillig, R.J., Fletcher, R.T., Somers, R.L., Chader, G.J. Exp. Eye Res. (1988) [Pubmed]
  17. Enhancement and inhibition of mitogenic action of insulin-like growth factor I by high glucose in cultured bovine retinal pericytes. Naruse, K., Sakakibara, F., Nakamura, J., Koh, N., Hotta, N. Life Sci. (1996) [Pubmed]
  18. Expression of IGF receptors on alveolar macrophages: IGF-induced changes in InsPi formation, [Ca2+]i, and pHi. Geertz, R., Kiess, W., Kessler, U., Hoeflich, A., Tarnok, A., Gercken, G. Mol. Cell. Biochem. (1997) [Pubmed]
  19. Chromaffin cells express two types of insulin-like growth factor receptors. Danielsen, A., Larsen, E., Gammeltoft, S. Brain Res. (1990) [Pubmed]
  20. Analysis of mRNA transcripts for insulin-like growth factor receptors and binding proteins in bovine embryos derived from somatic cell nuclear transfer. Sawai, K., Kageyama, S., Moriyasu, S., Hirayama, H., Minamihashi, A., Onoe, S. Cloning Stem Cells (2005) [Pubmed]
  21. Neurogenesis in explants from the walls of the lateral ventricle of adult bovine brain: role of endogenous IGF-1 as a survival factor. Pérez-Martín, M., Cifuentes, M., Grondona, J.M., Bermúdez-Silva, F.J., Arrabal, P.M., Pérez-Fígares, J.M., Jiménez, A.J., García-Segura, L.M., Férnandez-Llebrez, P. Eur. J. Neurosci. (2003) [Pubmed]
  22. Linkage mapping of the bovine insulin-like growth factor-1 receptor gene. Moody, D.E., Pomp, D., Barendse, W. Mamm. Genome (1996) [Pubmed]
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