Insulin-like growth factor-binding protein

The insulin-like growth factor-binding protein (IGFBP) serves as a transport protein for insulin-like growth factor 1 (IGF-1).[2]

Insulin-like growth factor
binding protein
Structure of the IGF-binding domain of the insulin-like growth factor-binding protein-5 (IGFBP-5)[1]
Identifiers
SymbolIGFBP
PfamPF00219
InterProIPR000867
SMARTSM00121
PROSITEPDOC00194
SCOPe1boe / SUPFAM

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.[3]

The IGFBPs help to lengthen the half-life of circulating IGFs in all tissues, including the prostate.[4] 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.[5] 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:

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See also

References
  1. Kalus W, Zweckstetter M, Renner C, et al. (November 1998). "Structure of the IGF-binding domain of the insulin-like growth factor-binding protein-5 (IGFBP-5): implications for IGF and IGF-I receptor interactions" (PDF). EMBO J. 17 (22): 6558–72. doi:10.1093/emboj/17.22.6558. PMC 1171003. PMID 9822601.
  2. Hwa V, Oh Y, Rosenfeld RG (December 1999). "The insulin-like growth factor-binding protein (IGFBP) superfamily". Endocr. Rev. 20 (6): 761–87. doi:10.1210/er.20.6.761. PMID 10605625.
  3. Clemmons DR, Busby WH, Arai T, Nam TJ, Clarke JB, Jones JI, Ankrapp DK (1995). "Role of insulin-like growth factor binding proteins in the control of IGF actions". Prog. Growth Factor Res. 6 (2–4): 357–66. doi:10.1016/0955-2235(95)00013-5. PMID 8817679.
  4. Stewart CE, Bates PC, Calder TA, Woodall SM, Pell JM (September 1993). "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. doi:10.1210/en.133.3.1462. PMID 7689959.
  5. Gregory CW, DeGeorges A, Sikes RA (2001). "The IGF axis in the development and progression of prostate cancer". Recent Research Developments in Cancer: 437–462. ISBN 81-7895-002-2.
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