Role of Insulin-like Growth Factor Binding Proteins in Modulating Insulin-like Growth Factor Action
The insulin-like growth factor (IGF) binding proteins are high affinity, soluble carrier proteins that are present in all extracellular fluids. Six structurally distinct forms of IGF binding proteins have been cloned and their cDNA sequences determined (Shimasaki et al. 1991). Although all six share structural homology many of their features appear to be distinct. Structural characterization and purification of these proteins has made it possible to more rationally discern the molecular mechanisms by which they function to modify IGF actions. All six proteins have been shown to contain a highly conserved cysteine pattern and disruption of any of the disulfide linkages appears to lead to a substantial loss in IGF binding capacity, suggesting that the cysteine linkage pattern is necessary to form the correct tertiary structure for maximum IGF binding (Brinkman et al. 1991). Structural characterization has also shown that numerous post-translational modifications of these proteins can occur. Specifically IGFBP-1 through 5 have been shown to be proteolytically cleaved. These proteases exist in a variety of physiologic fluids and therefore are capable of modifying binding protein activity by eliminating IGF binding following proteolytic cleavage. In addition each of these proteins appears to be glycosylated. The functional significance of glycosylation has not been determined at the present time. Finally several of the proteins appear to be phosphorylated. The biologic significance of phosphorylation has been determined in the case of IGFBP-1 where it has been shown to modulate both IGF binding affinity and cellular responsiveness to this growth factor.
KeywordsPermeability Estrogen Cysteine Serine Half Life
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