Insulin-like growth factor binding protein proteolysis in bone cell models.

Insulin-like growth factor binding protein (IGFBP) proteases-their identification, regulation, and biological significance-are currently an area of ardent investigation. This has developed from the very recent realization that IGFBP availability and bioactivity is determined not only by gene expression, but also by the controlled proteolytic processing of the protein in the pericellular environment. In each case identified so far, the modified IGFBP acts dramatically different from native or recombinant IGFBP in solution. This post-translational modification of IGFBP structure/function could have widespread significance since IGFBPs modulate the diverse growth-promoting activities of the IGFs. In fact, it may be argued that local IGF action is largely controlled by this mechanism. Therefore, knowledge of the form, function, and control of the various IGFBP proteases is likely to have major implications for our understanding of the physiology and pathophysiology of the IGFs.