F
IPR022326

Insulin-like growth factor-binding protein 6

InterPro entry
Short nameIGFBP-6
Overlapping
homologous
superfamilies
 
family relationships

Description

Insulin-like growth factors (IGFs)-I and -II are small secreted peptides that stimulate the survival, and promote the proliferation and differentiation, of many cell types
[1]
. In biological fluids, these growth factors are usually bound to IGF binding proteins (IGFBPs), which regulate their availability and activity by prolonging their half-life and modulating their receptor interactions.

To date, six IGFBP family members have been identified (termed IGFBP1-6)
[2]
. They share a conserved gene (intron-exon) organisation and high IGF binding affinity. Structurally, the proteins also share a common domain architecture, possessing a conserved N-terminal IGFBP domain, a highly variable mid-section, and a thyroglobulin type-1 (Tg1) domain in their C-terminal regions.

In addition to their role in the regulation of IGF activity, there is evidence for the direct association of IGFBPs with a variety of extracellular and cell surface molecules
[3, 4]
, with consequent effects upon important biological processes. These include modulation of bone cell proliferation
[5]
, and growth arrest of breast and prostate cancer cells
[3, 6]
.

IGFBP6 is a potent inducer of programmed cell death in lung cancer cells
[7]
. The protein may therefore represent a potential target as a cancer therapeutic.

References

1.Growth, differentiation, and survival: multiple physiological functions for insulin-like growth factors. Stewart CE, Rotwein P. Physiol. Rev. 76, 1005-26, (1996). PMID: 8874492

2.The insulin-like growth factor-binding protein (IGFBP) superfamily. Hwa V, Oh Y, Rosenfeld RG. Endocr. Rev. 20, 761-87, (1999). View articlePMID: 10605625

3.Demonstration of receptors for insulin-like growth factor binding protein-3 on Hs578T human breast cancer cells. Oh Y, Muller HL, Pham H, Rosenfeld RG. J. Biol. Chem. 268, 26045-8, (1993). PMID: 7504671

4.Heparin modulates the binding of insulin-like growth factor (IGF) binding protein-5 to a membrane protein in osteoblastic cells. Andress DL. J. Biol. Chem. 270, 28289-96, (1995). PMID: 7499327

5.Studies on the mechanisms by which insulin-like growth factor (IGF) binding protein-4 (IGFBP-4) and IGFBP-5 modulate IGF actions in bone cells. Mohan S, Nakao Y, Honda Y, Landale E, Leser U, Dony C, Lang K, Baylink DJ. J. Biol. Chem. 270, 20424-31, (1995). View articlePMID: 7544787

6.Insulin-like growth factor (IGF)-binding protein-3 induces apoptosis and mediates the effects of transforming growth factor-beta1 on programmed cell death through a p53- and IGF-independent mechanism. Rajah R, Valentinis B, Cohen P. J. Biol. Chem. 272, 12181-8, (1997). View articlePMID: 9115291

7.Insulin-like growth factor binding protein-6 activates programmed cell death in non-small cell lung cancer cells. Sueoka N, Lee HY, Wiehle S, Cristiano RJ, Fang B, Ji L, Roth JA, Hong WK, Cohen P, Kurie JM. Oncogene 19, 4432-6, (2000). View articlePMID: 10980619

GO terms

biological process

  • None
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