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Gene Review

Igf1r  -  insulin-like growth factor I receptor

Mus musculus

Synonyms: A330103N21Rik, CD221, D930020L01, IGF-1R, IGF-I receptor, ...
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Disease relevance of Igf1r


Psychiatry related information on Igf1r

  • In rodents, IGF-I receptor impairment led to brain amyloidosis, cognitive disturbance, and hyperphosphorylated tau deposits together with other changes found in Alzheimer's disease such as gliosis and synaptic protein loss [5].

High impact information on Igf1r

  • To directly define the role of Igf1, we have created a mouse with a beta-cell-specific knockout of Igf1r (betaIgf1r(-/-)) [2].
  • Irs-2 coordinates Igf-1 receptor-mediated beta-cell development and peripheral insulin signalling [6].
  • In addition to generalized organ hypoplasia in Igf1r(-/-) embryos, including the muscles, and developmental delays in ossification, deviations from normalcy were observed in the central nervous system and epidermis [1].
  • The Igf1r(+/-) mice display greater resistance to oxidative stress, a known determinant of ageing [7].
  • The ability of the insulin receptor to act as a bona fide IGF-II-dependent growth promoter is underscored by its rescue of double knockout Igf1r/Igf2r mice [8].

Chemical compound and disease context of Igf1r


Biological context of Igf1r


Anatomical context of Igf1r

  • Fibroblast cell lines were established from mouse embryos homozygous for a targeted disruption of the Igf1r gene, encoding the type 1 receptor for insulin-like growth factor I (IGF-I) and from their wild-type littermates [19].
  • To examine the local actions of IGF signaling in skeletal tissue in a physiological context, we have used Cre-mediated recombination to disrupt selectively in mouse osteoblasts the gene encoding the type 1 IGF receptor (Igf1r) [20].
  • Here we show that the insulin receptor tyrosine kinase family, comprising Ir, Igf1r and Irr, is required for the appearance of male gonads and thus for male sexual differentiation [21].
  • Since hormonal activation of IRS-1 is epithelial, estrogen-specific, and initiated before maximal DNA synthesis occurs following treatment with hormone, this protein, as part of the IGF-1R pathway, may be important in mediating estrogen-stimulated proliferation in the uterus [22].
  • Furthermore, IGF-1R-null keratinocytes exhibit accelerated differentiation and decreased proliferation [16].

Associations of Igf1r with chemical compounds

  • The nonestrogenic steroid hormones examined did not stimulate the P-Tyr content of IGF-1R or IRS-1 [22].
  • In streptozotocin-induced diabetes, IGF-I receptor was up-regulated in the kidneys from decorin-null mice [23].
  • We conclude that the insulin receptor mediates some aspects of metabolic signaling in adipocytes more effectively than the IGF-I receptor, as a consequence of more efficient phosphorylation of IRS-1 and greater recruitment/activation of phosphoinositide 3-kinase [24].
  • In contrast, Zn(2+) increases the affinity by which either [(125)I]-IGF-I or [(125)I]-R(3)-IGF-I binds to the IGF-1R, but depresses [(125)I]-IGF-II binding to the IGF-type 2 receptor (IGF-2R) on BC(3)H-1 cells [25].
  • In addition, to determine whether IGF-II decreases IGF-I receptor expression by stimulating receptor protein degradation, pulse/chase experiments with [35S]methionine/cysteine were carried out [26].

Physical interactions of Igf1r


Enzymatic interactions of Igf1r


Regulatory relationships of Igf1r


Other interactions of Igf1r


Analytical, diagnostic and therapeutic context of Igf1r

  • This is the first study to give a complete overview of the mRNA expression patterns of Igf-1, Igf-2, type 1 Igf receptor (Igf1r) and six Igf binding proteins (IGFBP-1-6) in embryonic mouse limbs, at various stages of development, by whole mount in situ hybridization (ISH) [42].
  • By using a combined approach of conditional gene ablation and a three-dimensional organotypic model, we demonstrate that IGF-1R-deficient skin cocultures show abnormal maturation and differentiation patterns [16].
  • The IGF-1 receptor was detected immunohistochemically with antibodies to the IGF-1 receptor and visualized with conventional light microscopy and confocal laser scanning microscopy (CLSM) [43].
  • An increase in the expression of the IGF-1R in GHo cells was also detected by Western blot analysis, (125)I-IGF-1 binding and analysis of IGF-1R promoter luciferase constructs [34].
  • The absence of IGF-1R caused a significant decrease in hepatocyte proliferation in males (-52%), but not in females, as assessed by Ki67 immunohistochemistry [44].


  1. Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r). Liu, J.P., Baker, J., Perkins, A.S., Robertson, E.J., Efstratiadis, A. Cell (1993) [Pubmed]
  2. beta-cell-specific deletion of the Igf1 receptor leads to hyperinsulinemia and glucose intolerance but does not alter beta-cell mass. Kulkarni, R.N., Holzenberger, M., Shih, D.Q., Ozcan, U., Stoffel, M., Magnuson, M.A., Kahn, C.R. Nat. Genet. (2002) [Pubmed]
  3. Functional insulin and insulin-like growth factor-1 receptors are preferentially expressed in multiple myeloma cell lines as compared to B-lymphoblastoid cell lines. Freund, G.G., Kulas, D.T., Way, B.A., Mooney, R.A. Cancer Res. (1994) [Pubmed]
  4. IGF-1 receptor contributes to the malignant phenotype in human and canine osteosarcoma. MacEwen, E.G., Pastor, J., Kutzke, J., Tsan, R., Kurzman, I.D., Thamm, D.H., Wilson, M., Radinsky, R. J. Cell. Biochem. (2004) [Pubmed]
  5. Blockade of the insulin-like growth factor I receptor in the choroid plexus originates Alzheimer's-like neuropathology in rodents: new cues into the human disease? Carro, E., Trejo, J.L., Spuch, C., Bohl, D., Heard, J.M., Torres-Aleman, I. Neurobiol. Aging (2006) [Pubmed]
  6. Irs-2 coordinates Igf-1 receptor-mediated beta-cell development and peripheral insulin signalling. Withers, D.J., Burks, D.J., Towery, H.H., Altamuro, S.L., Flint, C.L., White, M.F. Nat. Genet. (1999) [Pubmed]
  7. IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Holzenberger, M., Dupont, J., Ducos, B., Leneuve, P., Géloën, A., Even, P.C., Cervera, P., Le Bouc, Y. Nature (2003) [Pubmed]
  8. Distinct and overlapping functions of insulin and IGF-I receptors. Nakae, J., Kido, Y., Accili, D. Endocr. Rev. (2001) [Pubmed]
  9. Insulin-like growth factor I gene expression is induced in astrocytes during experimental demyelination. Komoly, S., Hudson, L.D., Webster, H.D., Bondy, C.A. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  10. The matrix metalloproteinase-9 regulates the insulin-like growth factor-triggered autocrine response in DU-145 carcinoma cells. Mañes, S., Llorente, M., Lacalle, R.A., Gómez-Moutón, C., Kremer, L., Mira, E., Martínez-A, C. J. Biol. Chem. (1999) [Pubmed]
  11. Elevated levels of IGF-1 receptor convey invasive and metastatic capability in a mouse model of pancreatic islet tumorigenesis. Lopez, T., Hanahan, D. Cancer Cell (2002) [Pubmed]
  12. Inhibition of insulin/IGF-1 receptor signaling enhances bile acid toxicity in primary hepatocytes. Dent, P., Han, S.I., Mitchell, C., Studer, E., Yacoub, A., Grandis, J., Grant, S., Krystal, G.W., Hylemon, P.B. Biochem. Pharmacol. (2005) [Pubmed]
  13. Nordihydroguaiaretic acid (NDGA) inhibits the IGF-1 and c-erbB2/HER2/neu receptors and suppresses growth in breast cancer cells. Youngren, J.F., Gable, K., Penaranda, C., Maddux, B.A., Zavodovskaya, M., Lobo, M., Campbell, M., Kerner, J., Goldfine, I.D. Breast Cancer Res. Treat. (2005) [Pubmed]
  14. Effects of mutations in the insulin-like growth factor signaling system on embryonic pancreas development and beta-cell compensation to insulin resistance. Kido, Y., Nakae, J., Hribal, M.L., Xuan, S., Efstratiadis, A., Accili, D. J. Biol. Chem. (2002) [Pubmed]
  15. Insulin-like growth factor I receptor gene is concordant with c-Fes protooncogene and mouse chromosome 7 in somatic cell hybrids. Sundaresan, S., Francke, U. Somat. Cell Mol. Genet. (1989) [Pubmed]
  16. Insulin-like growth factor 1 receptor signaling regulates skin development and inhibits skin keratinocyte differentiation. Sadagurski, M., Yakar, S., Weingarten, G., Holzenberger, M., Rhodes, C.J., Breitkreutz, D., Leroith, D., Wertheimer, E. Mol. Cell. Biol. (2006) [Pubmed]
  17. Insulin-like growth factor-1 (IGF-1) receptor-insulin receptor substrate complexes in the uterus. Altered signaling response to estradiol in the IGF-1(m/m) mouse. Richards, R.G., Walker, M.P., Sebastian, J., DiAugustine, R.P. J. Biol. Chem. (1998) [Pubmed]
  18. Susceptibility to apoptosis in insulin-like growth factor-I receptor-deficient brown adipocytes. Valverde, A.M., Mur, C., Brownlee, M., Benito, M. Mol. Biol. Cell (2004) [Pubmed]
  19. Simian virus 40 large tumor antigen is unable to transform mouse embryonic fibroblasts lacking type 1 insulin-like growth factor receptor. Sell, C., Rubini, M., Rubin, R., Liu, J.P., Efstratiadis, A., Baserga, R. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  20. Osteoblast-specific knockout of the insulin-like growth factor (IGF) receptor gene reveals an essential role of IGF signaling in bone matrix mineralization. Zhang, M., Xuan, S., Bouxsein, M.L., von Stechow, D., Akeno, N., Faugere, M.C., Malluche, H., Zhao, G., Rosen, C.J., Efstratiadis, A., Clemens, T.L. J. Biol. Chem. (2002) [Pubmed]
  21. Testis determination requires insulin receptor family function in mice. Nef, S., Verma-Kurvari, S., Merenmies, J., Vassalli, J.D., Efstratiadis, A., Accili, D., Parada, L.F. Nature (2003) [Pubmed]
  22. Estradiol stimulates tyrosine phosphorylation of the insulin-like growth factor-1 receptor and insulin receptor substrate-1 in the uterus. Richards, R.G., DiAugustine, R.P., Petrusz, P., Clark, G.C., Sebastian, J. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  23. Decorin-mediated regulation of fibrillin-1 in the kidney involves the insulin-like growth factor-I receptor and Mammalian target of rapamycin. Schaefer, L., Tsalastra, W., Babelova, A., Baliova, M., Minnerup, J., Sorokin, L., Gr??ne, H.J., Reinhardt, D.P., Pfeilschifter, J., Iozzo, R.V., Schaefer, R.M. Am. J. Pathol. (2007) [Pubmed]
  24. Differences in signaling properties of the cytoplasmic domains of the insulin receptor and insulin-like growth factor receptor in 3T3-L1 adipocytes. Ursø, B., Cope, D.L., Kalloo-Hosein, H.E., Hayward, A.C., Whitehead, J.P., O'Rahilly, S., Siddle, K. J. Biol. Chem. (1999) [Pubmed]
  25. Zinc partitions insulin-like growth factors (IGFs) from soluble IGF binding protein (IGFBP)-5 to the cell surface receptors of BC3H-1 muscle cells. McCusker, R.H., Novakofski, J. J. Cell. Physiol. (2003) [Pubmed]
  26. Mechanisms of insulin-like growth factor (IGF)-II-induced IGF-I receptor down-regulation in BC3H-1 muscle cells. Rosenthal, S.M., Brown, E.J. J. Endocrinol. (1994) [Pubmed]
  27. Structural determinants for high-affinity binding of insulin-like growth factor II to insulin receptor (IR)-A, the exon 11 minus isoform of the IR. Denley, A., Bonython, E.R., Booker, G.W., Cosgrove, L.J., Forbes, B.E., Ward, C.W., Wallace, J.C. Mol. Endocrinol. (2004) [Pubmed]
  28. Zinc partitions IGFs from soluble IGF binding proteins (IGFBP)-5, but not soluble IGFBP-4, to myoblast IGF type 1 receptors. McCusker, R.H., Novakofski, J. J. Endocrinol. (2004) [Pubmed]
  29. Lipid rafts/caveolae are essential for insulin-like growth factor-1 receptor signaling during 3T3-L1 preadipocyte differentiation induction. Huo, H., Guo, X., Hong, S., Jiang, M., Liu, X., Liao, K. J. Biol. Chem. (2003) [Pubmed]
  30. Effect of receptor phosphorylation on the binding between IRS-1 and IGF-1R as revealed by surface plasmon resonance biosensor. Huang, M., Lai, W.P., Wong, M.S., Yang, M. FEBS Lett. (2001) [Pubmed]
  31. Mechanisms of cell cycle arrest by methylseleninic acid. Zhu, Z., Jiang, W., Ganther, H.E., Thompson, H.J. Cancer Res. (2002) [Pubmed]
  32. Differential roles of the insulin and insulin-like growth factor-I (IGF-I) receptors in response to insulin and IGF-I. Entingh-Pearsall, A., Kahn, C.R. J. Biol. Chem. (2004) [Pubmed]
  33. c-myc-induced hepatocarcinogenesis in the absence of IGF-I receptor. Cadoret, A., Desbois-Mouthon, C., Wendum, D., Leneuve, P., Perret, C., Tronche, F., Housset, C., Holzenberger, M. Int. J. Cancer (2005) [Pubmed]
  34. Expression of insulin-like growth factor-1 and insulin-like growth factor-1 receptors in EL4 lymphoma cells overexpressing growth hormone. Weigent, D.A., Arnold, R.E. Cell. Immunol. (2005) [Pubmed]
  35. Suppressor of cytokine signaling 1 suppresses muscle differentiation through modulation of IGF-I receptor signal transduction. Inaba, M., Saito, H., Fujimoto, M., Sumitani, S., Ohkawara, T., Tanaka, T., Kouhara, H., Kasayama, S., Kawase, I., Kishimoto, T., Naka, T. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  36. The hypothalamic insulin-like growth factor-1 receptor and its relationship to gonadotropin-releasing hormones neurones during postnatal development. Daftary, S.S., Gore, A.C. J. Neuroendocrinol. (2004) [Pubmed]
  37. Insulin-like growth factor II acts through an endogenous growth pathway regulated by imprinting in early mouse embryos. Rappolee, D.A., Sturm, K.S., Behrendtsen, O., Schultz, G.A., Pedersen, R.A., Werb, Z. Genes Dev. (1992) [Pubmed]
  38. Protein kinase B/AKT 1 plays a pivotal role in insulin-like growth factor-1 receptor signaling induced 3T3-L1 adipocyte differentiation. Xu, J., Liao, K. J. Biol. Chem. (2004) [Pubmed]
  39. Growth hormone receptor gene deficiency causes delayed insulin responsiveness in skeletal muscles without affecting compensatory islet cell overgrowth in obese mice. Robertson, K., Kopchick, J.J., Liu, J.L. Am. J. Physiol. Endocrinol. Metab. (2006) [Pubmed]
  40. Castration rapidly decreases local insulin-like growth factor-1 levels and inhibits its effects in the ventral prostate in mice. Ohlson, N., Bergh, A., Persson, M.L., Wikstr??m, P. Prostate (2006) [Pubmed]
  41. Meg1/Grb10 overexpression causes postnatal growth retardation and insulin resistance via negative modulation of the IGF1R and IR cascades. Shiura, H., Miyoshi, N., Konishi, A., Wakisaka-Saito, N., Suzuki, R., Muguruma, K., Kohda, T., Wakana, S., Yokoyama, M., Ishino, F., Kaneko-Ishino, T. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  42. mRNA expression patterns of the IGF system during mouse limb bud development, determined by whole mount in situ hybridization. van Kleffens, M., Groffen, C., Rosato, R.R., van den Eijnde, S.M., van Neck, J.W., Lindenbergh-Kortleve, D.J., Zwarthoff, E.C., Drop, S.L. Mol. Cell. Endocrinol. (1998) [Pubmed]
  43. Localization and quantification of the insulin-like growth factor-1 receptor in mouse articular cartilage by confocal laser scanning microscopy. Verschure, P.J., van Marle, J., Joosten, L.A., Van den Berg, W.B. J. Histochem. Cytochem. (1994) [Pubmed]
  44. Hepatocyte proliferation during liver regeneration is impaired in mice with liver-specific IGF-1R knockout. Desbois-Mouthon, C., Wendum, D., Cadoret, A., Rey, C., Leneuve, P., Blaise, A., Housset, C., Tronche, F., Le Bouc, Y., Holzenberger, M. FASEB J. (2006) [Pubmed]
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