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Gene Review

IGFBP2  -  insulin-like growth factor binding protein...

Homo sapiens

Synonyms: BP2, IBP-2, IBP2, IGF-BP53, IGF-binding protein 2, ...
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Disease relevance of IGFBP2


Psychiatry related information on IGFBP2


High impact information on IGFBP2

  • Other myoblasts also secrete IGFBP-2 [12].
  • As a result, chronically elevated fasting and postprandial insulin levels may lead to a decrease in circulating IGFBP-1 and IGFBP-2 concentrations and, consequently, an increase in IGF-I bioavailability [13].
  • Thus, IGFBP-2 may facilitate the targeting of IGFs, and in particular IGF-IIE, to skeletal tissue in HCAO patients, with a subsequent stimulation by IGFs of osteoblast function [14].
  • Of the IGFBPs, an increase in IGFBP-2 was unique to these patients and was not found in control hepatitis C or hepatitis B patients [14].
  • We also tested the ability of IGFBP-2, a related binding protein which has an arginine-glycine-aspartate sequence but does not associate with integrin family members, to enhance IGF-I bioactivity [15].

Chemical compound and disease context of IGFBP2


Biological context of IGFBP2


Anatomical context of IGFBP2


Associations of IGFBP2 with chemical compounds

  • Among the genes that were exclusively changed by treatment with the antisense AR ODN were the insulin-like growth factor binding protein 2 (IGFBP2) and the phosphatidylinositol-4-phosphate 5-kinase type I alpha (PIP5KIA) [25].
  • Its 38 NH2-terminal amino acids are identical to those of an IGFBP sequence derived from a human cDNA that cross-hybridizes with the rat IGFBP-2 cDNA [26].
  • Pretreatment serum IGFBP-2 and IGFBP-6 levels were greatly elevated, but as glucose normalized with treatment, only IGFBP-2 decreased, showing an inverse correlation with glucose (r = 0.716) [27].
  • IGFBP-2 production was inhibited by hCG (100 ng/mL) to 32 +/- 8% of levels in control cultures; a similar inhibition was seen with dibutyryl cAMP and forskolin, but not with FSH [28].
  • The binding of IGFBP-2 to heparin was detectable using an IGF-I to IGFBP-2 molar ratio of 2:1 [29].
  • Basal, IGF-, or estradiol-stimulated IGFBP-2 was abrogated by LY294002 and rapamycin and an inhibitor of IGFR1 tyrosine kinase activity, AG1024 [30].

Physical interactions of IGFBP2

  • During IGF I infusion, IGFBP-3 appears in the small complex whose IGFBP-2 and IGF I increase three- to fivefold and fivefold, respectively [31].
  • Here, we show that point mutations in three individual NLSs, NLS1, NLS2, and a novel accessory NLS, NLSa, do not block nuclear translocation, but compromise the ability of menin to repress expression of the endogenous insulin-like growth factor binding protein-2 (IGFBP-2) gene [32].
  • IGFBP-2 is a form of binding protein that is structurally distinct from IGFBP-1 [33].
  • In this study, we assessed the potential role of insulin-like growth factor-I (IGF-I), the IGF-I receptor (IGF-IR) and IGF binding protein-2 (IGFBP-2) in human colorectal cancer [34].
  • Fibroblast growth factor-2 inhibits the maturation of pro-insulin-like growth factor-II (Pro-IGF-II) and the expression of insulin-like growth factor binding protein-2 (IGFBP-2) in the human adrenocortical tumor cell line NCI-H295R [35].

Regulatory relationships of IGFBP2

  • IGFBP-2 production was also inhibited by IGF-II and [Leu27]IGF-II (ED50 for both 3 ng/mL) but not by IGF-I at up to 30 ng/mL [28].
  • The mature UD expressed IGFBP-3 mRNA while the ampulla in contact with the MB lacked IGFBP-3 mRNA and expressed IGFBP-2 exclusively [36].
  • All IGFBP-secreting cell lines expressed the IGFBP-2 gene as determined by Northern blot analysis [37].
  • The IGFBP-2 concentrations were also suppressed in obese subjects and inversely related to free IGF-1 (r = -0.48, P = 0.001) [38].
  • We conclude that prostatic stromal cell strains isolated from patients with BPH hyperexpress the mRNA for IGF-II and IGFBP-5 while expressing reduced amounts of IGFBP-2 mRNA [39].
  • Further supporting the inter-relationship between IGFBP-2 and CD24, knockdown of IGFBP-2 suppressed the CD24 promoter activity [40].

Other interactions of IGFBP2

  • The proportion of IGF-I associated with IGFBP-3 remained constant throughout life, but was significantly lower in GHD due to an increase in IGF-I/IGFBP-2 complexes [41].
  • IGFBP-2 mRNA was the most abundant IGFBP mRNA in the human ovary [42].
  • In the controls, IGF-II was associated primarily with IGFBP-3 and to a lesser extent with IGFBP-2, whereas in GHD the reverse was found [41].
  • Osteoarthritic cartilage samples produced IGFBP-2, -3, and -4; glycosylated IGFBP-4; and IGFBP-5 [43].
  • Changes in IGFBP-2, free IGF-1, and total IGF-1 responses were minimal and did not differ significantly from those during the 4-h fast [44].

Analytical, diagnostic and therapeutic context of IGFBP2

  • Northern blot analysis revealed IGFBP-2 and -4 mRNA in all ovarian compartments and IGFBP-5 mRNA in stroma and theca [42].
  • Immunoblotting identified this 32-kDa band together with a proteolytic fragment of 25 kDa as IGFBP-2, and quantitative analysis showed significantly higher levels of total IGFBP-2 in malignant tumors than in benign tumors (P < 0.001) [45].
  • A 31-33 kilodalton (kDa) doublet identified as IGFBP-2 by immunoprecipitation was consistently seen and was shown by metabolic labeling to be synthesized de novo [28].
  • MFO-36 cells produced IGFBPs of 34 kDa and 50 kDa as determined by SDS-PAGE, and the cells expressed mRNAs for IGFBP-2, -3, -4, and -6 [46].
  • The purpose of this study is to examine the diagnostic and prognostic significance of elevated IGFBP-2 levels in children with AML after hematopoietic stem cell transplantation (HSCT) at relapse and continuous complete remission (CCR) [47].


  1. Free insulin-like growth factor (IGF)-I and IGF binding proteins 2, 5, and 6 in spinal motor neurons in amyotrophic lateral sclerosis. Wilczak, N., de Vos, R.A., De Keyser, J. Lancet (2003) [Pubmed]
  2. Insulin-like growth factor binding protein 2 enhances glioblastoma invasion by activating invasion-enhancing genes. Wang, H., Wang, H., Shen, W., Huang, H., Hu, L., Ramdas, L., Zhou, Y.H., Liao, W.S., Fuller, G.N., Zhang, W. Cancer Res. (2003) [Pubmed]
  3. Expression profiling of synovial sarcoma by cDNA microarrays: association of ERBB2, IGFBP2, and ELF3 with epithelial differentiation. Allander, S.V., Illei, P.B., Chen, Y., Antonescu, C.R., Bittner, M., Ladanyi, M., Meltzer, P.S. Am. J. Pathol. (2002) [Pubmed]
  4. Insulin-like growth factor 2 and insulin-like growth factor binding protein 2 expression in hepatoblastoma. Akmal, S.N., Yun, K., MacLay, J., Higami, Y., Ikeda, T. Hum. Pathol. (1995) [Pubmed]
  5. Expression of insulin-like growth factor-binding protein 2 in melanocytic lesions. Wang, H., Shen, S.S., Wang, H., Diwan, A.H., Zhang, W., Fuller, G.N., Prieto, V.G. J. Cutan. Pathol. (2003) [Pubmed]
  6. High serum IGFBP-2 is predictive of increased bone turnover in aging men and women. Amin, S., Riggs, B.L., Melton, L.J., Achenbach, S.J., Atkinson, E.J., Khosla, S. J. Bone Miner. Res. (2007) [Pubmed]
  7. Insulin-like growth factor binding protein-2 as a regulator of IGF actions in CNS: implications in multiple sclerosis. Chesik, D., De Keyser, J., Wilczak, N. Cytokine Growth Factor Rev. (2007) [Pubmed]
  8. Insulin-like growth factor binding protein-2 is a novel therapeutic target associated with breast cancer. So, A.I., Levitt, R.J., Eigl, B., Fazli, L., Muramaki, M., Leung, S., Cheang, M.C., Nielsen, T.O., Gleave, M., Pollak, M. Clin. Cancer Res. (2008) [Pubmed]
  9. Plasma IGFBP-2 levels predict clinical outcomes of patients with high-grade gliomas. Lin, Y., Jiang, T., Zhou, K., Xu, L., Chen, B., Li, G., Qiu, X., Jiang, T., Zhang, W., Song, S.W. Neuro-oncology (2009) [Pubmed]
  10. Effects of recombinant human insulin-like growth factor (IGF)-I and estrogen administration on IGF-I, IGF binding protein (IGFBP)-2, and IGFBP-3 in anorexia nervosa: a randomized-controlled study. Grinspoon, S., Miller, K., Herzog, D., Clemmons, D., Klibanski, A. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  11. Determinants of circulating insulin-like growth factor (IGF)-I and IGF binding proteins 1-3 in premenopausal women: physical activity and anthropometry (Netherlands). Voskuil, D.W., Bueno de Mesquita, H.B., Kaaks, R., van Noord, P.A., Rinaldi, S., Riboli, E., Grobbee, D.E., Peeters, P.H. Cancer Causes Control (2001) [Pubmed]
  12. Growth hormone and the insulin-like growth factor system in myogenesis. Florini, J.R., Ewton, D.Z., Coolican, S.A. Endocr. Rev. (1996) [Pubmed]
  13. Insulin, insulin-like growth factor-I (IGF-I), IGF binding proteins, their biologic interactions, and colorectal cancer. Sandhu, M.S., Dunger, D.B., Giovannucci, E.L. J. Natl. Cancer Inst. (2002) [Pubmed]
  14. Insulin-like growth factor system abnormalities in hepatitis C-associated osteosclerosis. Potential insights into increasing bone mass in adults. Khosla, S., Hassoun, A.A., Baker, B.K., Liu, F., Zein, N.N., Whyte, M.P., Reasner, C.A., Nippoldt, T.B., Tiegs, R.D., Hintz, R.L., Conover, C.A. J. Clin. Invest. (1998) [Pubmed]
  15. Interaction between the insulin-like growth factor family and the integrin receptor family in tissue repair processes. Evidence in a rabbit ear dermal ulcer model. Galiano, R.D., Zhao, L.L., Clemmons, D.R., Roth, S.I., Lin, X., Mustoe, T.A. J. Clin. Invest. (1996) [Pubmed]
  16. Classification of human astrocytic gliomas on the basis of gene expression: a correlated group of genes with angiogenic activity emerges as a strong predictor of subtypes. Godard, S., Getz, G., Delorenzi, M., Farmer, P., Kobayashi, H., Desbaillets, I., Nozaki, M., Diserens, A.C., Hamou, M.F., Dietrich, P.Y., Regli, L., Janzer, R.C., Bucher, P., Stupp, R., de Tribolet, N., Domany, E., Hegi, M.E. Cancer Res. (2003) [Pubmed]
  17. An interaction between insulin-like growth factor-binding protein 2 (IGFBP2) and integrin alpha5 is essential for IGFBP2-induced cell mobility. Wang, G.K., Hu, L., Fuller, G.N., Zhang, W. J. Biol. Chem. (2006) [Pubmed]
  18. Expression and down-regulation by retinoic acid of IGF binding protein-2 and -4 in medium from human neuroblastoma cells. Bernardini, S., Cianfarani, S., Spagnoli, A., Annicchiarico-Petruzzelli, M., Melino, G., Massoud, R., Boscherini, B., Finazzi-Agró, A., Rosenfeld, R.G., Federici, G. J. Neuroendocrinol. (1994) [Pubmed]
  19. Efficacy of octreotide-LAR in dieting women with abdominal obesity and polycystic ovary syndrome. Gambineri, A., Patton, L., De Iasio, R., Cantelli, B., Cognini, G.E., Filicori, M., Barreca, A., Diamanti-Kandarakis, E., Pagotto, U., Pasquali, R. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  20. Insulin-like growth factor-II and its binding proteins in placental development. Zhou, J., Bondy, C. Endocrinology (1992) [Pubmed]
  21. Structure and localization of the human insulin-like growth factor-binding protein 2 gene. Ehrenborg, E., Vilhelmsdotter, S., Bajalica, S., Larsson, C., Stern, I., Koch, J., Brøndum-Nielsen, K., Luthman, H. Biochem. Biophys. Res. Commun. (1991) [Pubmed]
  22. Expression of insulin-like growth factor mitogenic signals in adult soft-tissue sarcomas: significant correlation with malignant potential. Busund, L.T., Ow, K.T., Russell, P., Crowe, P.J., Yang, J.L. Virchows Arch. (2004) [Pubmed]
  23. Identification of insulin-like growth factor-binding protein-3 (IGFBP-3) and IGFBP-2 in human follicular fluid. Giudice, L.C., Farrell, E.M., Pham, H., Rosenfeld, R.G. J. Clin. Endocrinol. Metab. (1990) [Pubmed]
  24. Secretion of insulin-like growth factors and their binding proteins by human normal and hyperplastic prostatic cells in primary culture. Boudon, C., Rodier, G., Lechevallier, E., Mottet, N., Barenton, B., Sultan, C. J. Clin. Endocrinol. Metab. (1996) [Pubmed]
  25. Gene expression changes following androgen receptor elimination in LNCaP prostate cancer cells. Eder, I.E., Haag, P., Basik, M., Mousses, S., Bektic, J., Bartsch, G., Klocker, H. Mol. Carcinog. (2003) [Pubmed]
  26. Isolation from adult human serum of four insulin-like growth factor (IGF) binding proteins and molecular cloning of one of them that is increased by IGF I administration and in extrapancreatic tumor hypoglycemia. Zapf, J., Kiefer, M., Merryweather, J., Musiarz, F., Bauer, D., Born, W., Fischer, J.A., Froesch, E.R. J. Biol. Chem. (1990) [Pubmed]
  27. Regulation of the insulin-like growth factors and their binding proteins by glucocorticoid and growth hormone in nonislet cell tumor hypoglycemia. Baxter, R.C., Holman, S.R., Corbould, A., Stranks, S., Ho, P.J., Braund, W. J. Clin. Endocrinol. Metab. (1995) [Pubmed]
  28. Regulation of insulin-like growth factor binding protein production by human luteinizing granulosa cells cultured in defined medium. Cataldo, N.A., Woodruff, T.K., Giudice, L.C. J. Clin. Endocrinol. Metab. (1993) [Pubmed]
  29. Binding of insulin-like growth factor (IGF) I or II to IGF-binding protein-2 enables it to bind to heparin and extracellular matrix. Arai, T., Busby, W., Clemmons, D.R. Endocrinology (1996) [Pubmed]
  30. Expression of insulin-like growth factor binding protein-2 by MCF-7 breast cancer cells is regulated through the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway. Martin, J.L., Baxter, R.C. Endocrinology (2007) [Pubmed]
  31. Regulation of binding proteins for insulin-like growth factors (IGF) in humans. Increased expression of IGF binding protein 2 during IGF I treatment of healthy adults and in patients with extrapancreatic tumor hypoglycemia. Zapf, J., Schmid, C., Guler, H.P., Waldvogel, M., Hauri, C., Futo, E., Hossenlopp, P., Binoux, M., Froesch, E.R. J. Clin. Invest. (1990) [Pubmed]
  32. Tumor suppressor menin: the essential role of nuclear localization signal domains in coordinating gene expression. La, P., Desmond, A., Hou, Z., Silva, A.C., Schnepp, R.W., Hua, X. Oncogene (2006) [Pubmed]
  33. Three distinct forms of insulin-like growth factor binding proteins are released by decidual cells in culture. Clemmons, D.R., Thrailkill, K.M., Handwerger, S., Busby, W.H. Endocrinology (1990) [Pubmed]
  34. Role of insulin-like growth factor-I (IGF-I) receptor, IGF-I, and IGF binding protein-2 in human colorectal cancers. Mishra, L., Bass, B., Ooi, B.S., Sidawy, A., Korman, L. Growth Horm. IGF Res. (1998) [Pubmed]
  35. Fibroblast growth factor-2 inhibits the maturation of pro-insulin-like growth factor-II (Pro-IGF-II) and the expression of insulin-like growth factor binding protein-2 (IGFBP-2) in the human adrenocortical tumor cell line NCI-H295R. Boulle, N., Gicquel, C., Logié, A., Christol, R., Feige, J.J., Le Bouc, Y. Endocrinology (2000) [Pubmed]
  36. Expression of insulin-like growth factor and binding protein genes during nephrogenesis. Matsell, D.G., Delhanty, P.J., Stepaniuk, O., Goodyear, C., Han, V.K. Kidney Int. (1994) [Pubmed]
  37. Insulin-like growth-factor-binding protein gene expression and protein production by human tumour cell lines. Reeve, J.G., Kirby, L.B., Brinkman, A., Hughes, S.A., Schwander, J., Bleehen, N.M. Int. J. Cancer (1992) [Pubmed]
  38. Effect of obesity on total and free insulin-like growth factor (IGF)-1, and their relationship to IGF-binding protein (BP)-1, IGFBP-2, IGFBP-3, insulin, and growth hormone. Nam, S.Y., Lee, E.J., Kim, K.R., Cha, B.S., Song, Y.D., Lim, S.K., Lee, H.C., Huh, K.B. Int. J. Obes. Relat. Metab. Disord. (1997) [Pubmed]
  39. Insulin-like growth factor axis abnormalities in prostatic stromal cells from patients with benign prostatic hyperplasia. Cohen, P., Peehl, D.M., Baker, B., Liu, F., Hintz, R.L., Rosenfeld, R.G. J. Clin. Endocrinol. Metab. (1994) [Pubmed]
  40. Silencing of insulin-like growth factor-binding protein-2 in human glioblastoma cells reduces both invasiveness and expression of progression-associated gene CD24. Fukushima, T., Tezuka, T., Shimomura, T., Nakano, S., Kataoka, H. J. Biol. Chem. (2007) [Pubmed]
  41. Effect of severe growth hormone (GH) deficiency due to a mutation in the GH-releasing hormone receptor on insulin-like growth factors (IGFs), IGF-binding proteins, and ternary complex formation throughout life. Aguiar-Oliveira, M.H., Gill, M.S., de A Barretto, E.S., Alcântara, M.R., Miraki-Moud, F., Menezes, C.A., Souza, A.H., Martinelli, C.E., Pereira, F.A., Salvatori, R., Levine, M.A., Shalet, S.M., Camacho-Hubner, C., Clayton, P.E. J. Clin. Endocrinol. Metab. (1999) [Pubmed]
  42. Expression of insulin-like growth factor (IGF), IGF-binding protein, and IGF receptor messenger ribonucleic acids in normal and polycystic ovaries. Voutilainen, R., Franks, S., Mason, H.D., Martikainen, H. J. Clin. Endocrinol. Metab. (1996) [Pubmed]
  43. Chondrocytes from osteoarthritic cartilage have increased expression of insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) and -5, but not IGF-II or IGFBP-4. Olney, R.C., Tsuchiya, K., Wilson, D.M., Mohtai, M., Maloney, W.J., Schurman, D.J., Smith, R.L. J. Clin. Endocrinol. Metab. (1996) [Pubmed]
  44. The glycemic index of foods influences postprandial insulin-like growth factor-binding protein responses in lean young subjects. Brand-Miller, J.C., Liu, V., Petocz, P., Baxter, R.C. Am. J. Clin. Nutr. (2005) [Pubmed]
  45. Increased levels of insulin-like growth factor II (IGF-II) and IGF-binding protein-2 are associated with malignancy in sporadic adrenocortical tumors. Boulle, N., Logié, A., Gicquel, C., Perin, L., Le Bouc, Y. J. Clin. Endocrinol. Metab. (1998) [Pubmed]
  46. Production of insulin-like growth factor binding proteins by human ovarian carcinoma cells. Hofmann, J., Wegmann, B., Hackenberg, R., Kunzmann, R., Schulz, K.D., Havemann, K. J. Cancer Res. Clin. Oncol. (1994) [Pubmed]
  47. Elevated serum insulin-like growth factor binding protein-2 is associated with a high relapse risk after hematopoietic stem cell transplantation in childhood AML. Dawczynski, K., Kauf, E., Schlenvoigt, D., Gruhn, B., Fuchs, D., Zintl, F. Bone Marrow Transplant. (2006) [Pubmed]
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