Roles of insulin-like growth factor (IGF) binding proteins in regulating IGF actions

The insulin-like growth factor (IGF) system is an evolutionarily conserved signaling pathway that is composed of two IGF ligands, two IGF receptors, and six IGF binding proteins. Studies in a variety of species suggest that the IGF signaling system plays a fundamental role in regulating embryonic growth and differentiation as well as in maintaining homeostasis in the adults. In extracellular fluids, IGFs are present in a complex with an IGF-binding protein (IGFBP). These IGFBPs are traditionally thought to function as carrier proteins and regulate circulating IGF turnover, transport, and distribution. Locally expressed IGFBPs can also inhibit and/or potentiate IGF activities. Recent studies have shown that some IGFBPs, in particular IGFBP-3 and -5, possess intrinsic biological activities and can act through IGF-independent mechanisms. In this article, we provide a brief overview of our current understanding of the IGF signaling system with particular reference to IGFBPs.