Insulin-like growth factor-binding protein explained

The insulin-like growth factor-binding protein (IGFBP) serves as a transport protein for insulin-like growth factor 1 (IGF-1).^[1]

Function

Approximately 98% of IGF-1 is always bound to one of six binding proteins (IGF-BP). IGFBP-3, the most abundant protein, accounts for 80% of all IGF binding. IGF-1 binds to IGFBP-3 in a 1:1 molar ratio. IGF-BP also binds to IGF-1 inside the liver, allowing growth hormone to continuously act upon the liver to produce more IGF-1.

IGF binding proteins (IGFBPs) are proteins of 24 to 45 kDa. All six IGFBPs share 50% homology with each other and have binding affinities for IGF-I and IGF-II at the same order of magnitude as the ligands have for the IGF-IR.^[2]

The IGFBPs help to lengthen the half-life of circulating IGFs in all tissues, including the prostate.^[3] Individual IGFBPs may act to enhance or attenuate IGF signaling depending on their physiological context (i.e. cell type). Even with these similarities, some characteristics are different: chromosomal location, heparin binding domains, RGD recognition site, preference for binding IGF-I or IGF-II, and glycosylation and phosphorylation differences.^[4] These structural differences can have a tremendous impact on how the IGFBPs interact with cellular basement membranes.

Family members

In humans, IGFBPs are transcribed from the following seven genes:

• IGFBP1
• IGFBP2
• IGFBP3
• IGFBP4
• IGFBP5
• IGFBP6
• IGFBP7

See also

• Insulin-like growth factor receptor

Notes and References

1. Hwa V, Oh Y, Rosenfeld RG . The insulin-like growth factor-binding protein (IGFBP) superfamily . Endocr. Rev. . 20 . 6 . 761–87 . December 1999 . 10.1210/edrv.20.6.0382 . 10605625 . free .
2. Clemmons DR, Busby WH, Arai T, Nam TJ, Clarke JB, Jones JI, Ankrapp DK . Role of insulin-like growth factor binding proteins in the control of IGF actions . Prog. Growth Factor Res. . 6 . 2–4 . 357–66 . 1995 . 8817679 . 10.1016/0955-2235(95)00013-5.
3. Stewart CE, Bates PC, Calder TA, Woodall SM, Pell JM . Potentiation of insulin-like growth factor-I (IGF-I) activity by an antibody: supportive evidence for enhancement of IGF-I bioavailability in vivo by IGF binding proteins . Endocrinology . 133 . 3 . 1462–5 . September 1993 . 7689959 . 10.1210/endo.133.3.7689959.
4. Gregory CW, DeGeorges A, Sikes RA . The IGF axis in the development and progression of prostate cancer . Recent Research Developments in Cancer . 437–462 . 2001 . 81-7895-002-2.