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Gene Review

Igfbp3  -  insulin-like growth factor binding protein 3

Mus musculus

Synonyms: AI649005, IBP-3, IGF-binding protein 3, IGFBP-3, IGgfbp3, ...
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Disease relevance of Igfbp3


High impact information on Igfbp3

  • IGFBP-3 and -5 have carboxyl-terminal basic motifs incorporating heparin-binding and additional basic residues that interact with the cell surface and matrix, the nuclear transporter importin-beta, and other proteins [4].
  • Serine/threonine kinase receptors are proposed for IGFBP-3 and -5, but their signaling functions are poorly understood [4].
  • In serum, the majority of the IGFs exist in a 150-kDa complex including the IGF molecule, IGF binding protein 3 (IGFBP-3), and the acid labile subunit (ALS) [5].
  • These results demonstrate that IGF-I and IGFBP-3 may modulate the involutionary process of the lactating mammary gland [6].
  • Insulin-like growth factor-binding protein 3 messenger RNA was localized in the lamina propria [7].

Chemical compound and disease context of Igfbp3


Biological context of Igfbp3


Anatomical context of Igfbp3


Associations of Igfbp3 with chemical compounds


Physical interactions of Igfbp3

  • Gel retardation and reporter assays revealed that Runx1 binds to the promoter region of mouse IGFBP-3 gene and represses its transcription [24].
  • Thus, IGF-I/IGFBP-3 affords more efficient protection from insulitis, beta-cell destruction, and T1D than IGF-I, and this complex may represent an efficacious therapeutic treatment for the prevention of T1D [25].

Enzymatic interactions of Igfbp3


Regulatory relationships of Igfbp3


Other interactions of Igfbp3

  • IGFBP-3 and Nur77 are additive in inducing apoptosis [14].
  • Taken together, these data provide direct evidence for combinatorial effects of IGFBP-3, -4, and -5 in both metabolism and at least some soft tissues and strongly suggest overlapping roles for IGFBP-3 and -5 in maintaining IGF-I-mediated postnatal growth in mice [19].
  • New lines of knockout (KO) mice lacking either IGFBP-3, -4, or -5 had no apparent deficiencies in growth or metabolism beyond a modest growth impairment (approximately 85-90% of wild type) when IGFBP-4 was eliminated [19].
  • In the terminal end buds (TEBs), IGFBP-3 mRNA expression was consistent with its localization in the cap cells, whereas IGFBP-5 was highly expressed in the body cells of the TEB [17].
  • Overall, IGFBP-3 demonstrated the highest level of expression of any of the IGFBP genes throughout all the developmental stages studied [30].

Analytical, diagnostic and therapeutic context of Igfbp3

  • Immunohistochemistry revealed cytoplasmic localization of IGFBP-3 in the preponderance of preneoplastic and neoplastic esophageal lesions [1].
  • In cell culture systems insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) can both enhance and inhibit IGF-I action [31].
  • The 16-kDa fragment, isolated by HPLC following limited proteolysis of recombinant human (rh) IGFBP-3 by plasmin, in both assays dose-dependently (20 to 100 ng/ml) inhibited (up to 100%) maximal stimulation induced by 25 ng/ml bFGF, whereas intact IGFBP-3 had virtually no effect [32].
  • Protein levels of HB-EGF and insulin-like growth factor binding protein-3 (IGFBP-3), a molecule that stabilizes IGFs, which in turn helps to promote growth, were analyzed by Western blot [33].
  • The amount of IGFBP-3 present in pregnant serum after day 10 of gestation was not measurable by scanning laser densitometry [21].


  1. Epidermal growth factor receptor regulates aberrant expression of insulin-like growth factor-binding protein 3. Takaoka, M., Harada, H., Andl, C.D., Oyama, K., Naomoto, Y., Dempsey, K.L., Klein-Szanto, A.J., El-Deiry, W.S., Grimberg, A., Nakagawa, H. Cancer Res. (2004) [Pubmed]
  2. Perturbations in bone formation and resorption in insulin-like growth factor binding protein-3 transgenic mice. Silha, J.V., Mishra, S., Rosen, C.J., Beamer, W.G., Turner, R.T., Powell, D.R., Murphy, L.J. J. Bone Miner. Res. (2003) [Pubmed]
  3. Serum insulin-like growth factor binding protein-3 in the hypophosphatemic mouse: decreased activity and abnormal modulation by dietary phosphate. Moriwake, T., Abribat, T., Brazeau, P., Ecarot, B. J. Bone Miner. Res. (1995) [Pubmed]
  4. Cellular actions of the insulin-like growth factor binding proteins. Firth, S.M., Baxter, R.C. Endocr. Rev. (2002) [Pubmed]
  5. Circulating levels of IGF-1 directly regulate bone growth and density. Yakar, S., Rosen, C.J., Beamer, W.G., Ackert-Bicknell, C.L., Wu, Y., Liu, J.L., Ooi, G.T., Setser, J., Frystyk, J., Boisclair, Y.R., LeRoith, D. J. Clin. Invest. (2002) [Pubmed]
  6. Involution of the lactating mammary gland is inhibited by the IGF system in a transgenic mouse model. Neuenschwander, S., Schwartz, A., Wood, T.L., Roberts, C.T., Hennighausen, L., LeRoith, D. J. Clin. Invest. (1996) [Pubmed]
  7. Enhanced growth of small bowel in transgenic mice expressing human insulin-like growth factor I. Ohneda, K., Ulshen, M.H., Fuller, C.R., D'Ercole, A.J., Lund, P.K. Gastroenterology (1997) [Pubmed]
  8. Oral consumption of green tea polyphenols inhibits insulin-like growth factor-I-induced signaling in an autochthonous mouse model of prostate cancer. Adhami, V.M., Siddiqui, I.A., Ahmad, N., Gupta, S., Mukhtar, H. Cancer Res. (2004) [Pubmed]
  9. Inhibitory effect of a growth hormone receptor antagonist (G120K-PEG) on renal enlargement, glomerular hypertrophy, and urinary albumin excretion in experimental diabetes in mice. Flyvbjerg, A., Bennett, W.F., Rasch, R., Kopchick, J.J., Scarlett, J.A. Diabetes (1999) [Pubmed]
  10. Combination therapy of insulin-like growth factor binding protein-3 and retinoid X receptor ligands synergize on prostate cancer cell apoptosis in vitro and in vivo. Liu, B., Lee, K.W., Li, H., Ma, L., Lin, G.L., Chandraratna, R.A., Cohen, P. Clin. Cancer Res. (2005) [Pubmed]
  11. Regulation of metabolic water and protein compartments by insulin-like growth factor-I and testosterone in growth hormone-deficient lit/lit mice. Donahue, L.R., Watson, G., Beamer, W.G. J. Endocrinol. (1993) [Pubmed]
  12. In vivo suppression of hormone-refractory prostate cancer growth by inositol hexaphosphate: induction of insulin-like growth factor binding protein-3 and inhibition of vascular endothelial growth factor. Singh, R.P., Sharma, G., Mallikarjuna, G.U., Dhanalakshmi, S., Agarwal, C., Agarwal, R. Clin. Cancer Res. (2004) [Pubmed]
  13. Igfbp3 modulates cell proliferation in the hair follicle. Weger, N., Schlake, T. J. Invest. Dermatol. (2005) [Pubmed]
  14. Rapid apoptosis induction by IGFBP-3 involves an insulin-like growth factor-independent nucleomitochondrial translocation of RXRalpha/Nur77. Lee, K.W., Ma, L., Yan, X., Liu, B., Zhang, X.K., Cohen, P. J. Biol. Chem. (2005) [Pubmed]
  15. Involvement of insulin-like growth factor-I and insulin-like growth factor binding protein-3 in corneal fibroblasts during corneal wound healing. Izumi, K., Kurosaka, D., Iwata, T., Oguchi, Y., Tanaka, Y., Mashima, Y., Tsubota, K. Invest. Ophthalmol. Vis. Sci. (2006) [Pubmed]
  16. 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]
  17. Expression of the insulin-like growth factor binding proteins during postnatal development of the murine mammary gland. Allar, M.A., Wood, T.L. Endocrinology (2004) [Pubmed]
  18. Cellular patterns of insulin-like growth factor system gene expression in murine chondrogenesis and osteogenesis. Wang, E., Wang, J., Chin, E., Zhou, J., Bondy, C.A. Endocrinology (1995) [Pubmed]
  19. Diminished growth and enhanced glucose metabolism in triple knockout mice containing mutations of insulin-like growth factor binding protein-3, -4, and -5. Ning, Y., Schuller, A.G., Bradshaw, S., Rotwein, P., Ludwig, T., Frystyk, J., Pintar, J.E. Mol. Endocrinol. (2006) [Pubmed]
  20. Regulation of insulin-like growth factor binding protein secretion by a murine mammary epithelial cell line. Skaar, T.C., Baumrucker, C.R. Exp. Cell Res. (1993) [Pubmed]
  21. Characterization of insulin-like growth factor binding proteins (IGFBPs) during gestation in mice: effects of hypophysectomy and an IGFBP-specific serum protease activity. Fielder, P.J., Thordarson, G., Talamantes, F., Rosenfeld, R.G. Endocrinology (1990) [Pubmed]
  22. Insulin-Like growth factor I (IGF-I) and cyclic adenosine 3',5'-monophosphate regulate IGF-binding protein-3 gene expression by transcriptional and posttranscriptional mechanisms in mammary epithelial cells. Cohick, W.S., Wang, B., Verma, P., Boisclair, Y.R. Endocrinology (2000) [Pubmed]
  23. Molecular recognition characteristics in the insulin-like growth factor (IGF)-insulin-like growth factor binding protein -3/5 (IGFBP-3/5) heparin axis. Beattie, J., Phillips, K., Shand, J.H., Szymanowska, M., Flint, D.J., Allan, G.J. J. Mol. Endocrinol. (2005) [Pubmed]
  24. Runx1 promotes angiogenesis by downregulation of insulin-like growth factor-binding protein-3. Iwatsuki, K., Tanaka, K., Kaneko, T., Kazama, R., Okamoto, S., Nakayama, Y., Ito, Y., Satake, M., Takahashi, S., Miyajima, A., Watanabe, T., Hara, T. Oncogene (2005) [Pubmed]
  25. Insulin-like growth factor (IGF)-I/IGF-binding protein-3 complex: therapeutic efficacy and mechanism of protection against type 1 diabetes. Chen, W., Salojin, K.V., Mi, Q.S., Grattan, M., Meagher, T.C., Zucker, P., Delovitch, T.L. Endocrinology (2004) [Pubmed]
  26. Cloning and characterization of mouse klk27, a novel tissue kallikrein expressed in testicular Leydig cells and exhibiting chymotrypsin-like specificity. Matsui, H., Moriyama, A., Takahashi, T. Eur. J. Biochem. (2000) [Pubmed]
  27. Matrix metalloproteinase-7 degrades all insulin-like growth factor binding proteins and facilitates insulin-like growth factor bioavailability. Nakamura, M., Miyamoto, S., Maeda, H., Ishii, G., Hasebe, T., Chiba, T., Asaka, M., Ochiai, A. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  28. Tissue-specific expression of the insulin-like growth factor binding protein (IGFBP) mRNAs in mouse and rat development. Cerro, J.A., Grewal, A., Wood, T.L., Pintar, J.E. Regul. Pept. (1993) [Pubmed]
  29. Identification of insulin receptor substrate proteins as key molecules for the TbetaR-V/LRP-1-mediated growth inhibitory signaling cascade in epithelial and myeloid cells. Huang, S.S., Leal, S.M., Chen, C.L., Liu, I.H., Huang, J.S. FASEB J. (2004) [Pubmed]
  30. A quantitative RT-PCR study of the mRNA expression profile of the IGF axis during mammary gland development. Boutinaud, M., Shand, J.H., Park, M.A., Phillips, K., Beattie, J., Flint, D.J., Allan, G.J. J. Mol. Endocrinol. (2004) [Pubmed]
  31. Phenotypic manifestations of insulin-like growth factor-binding protein-3 overexpression in transgenic mice. Modric, T., Silha, J.V., Shi, Z., Gui, Y., Suwanichkul, A., Durham, S.K., Powell, D.R., Murphy, L.J. Endocrinology (2001) [Pubmed]
  32. The 16-kDa proteolytic fragment of insulin-like growth factor (IGF) binding protein-3 inhibits the mitogenic action of fibroblast growth factor on mouse fibroblasts with a targeted disruption of the type 1 IGF receptor gene. Zadeh, S.M., Binoux, M. Endocrinology (1997) [Pubmed]
  33. Heparin-binding EGF-like growth factor (HB-EGF) overexpression in transgenic mice downregulates insulin-like growth factor binding protein (IGFBP)-3 and -4 mRNA. Provenzano, A.P., Besner, G.E., James, P.F., Harding, P.A. Growth Factors (2005) [Pubmed]
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