GROWTH, DIFFERENTIATION, AND SURVIVAL - MULTIPLE PHYSIOLOGICAL FUNCTIONS FOR INSULIN-LIKE GROWTH-FACTORS

The insulin-like growth factors (IGFs), IGF-I and IGF-II, comprise a c onserved pair of secreted proteins with diverse effects on growth, dev elopment, and metabolism. Insulin-like growth factor action is initiat ed upon binding to cell-surface receptors and is modulated through int eractions with secreted IGF binding proteins (IGFBPs). The last decade has seen an explosion of new information about the physiological role s of the IGFs. In this review, we critically examine this information from biochemical, cell biological, and molecular genetic perspectives. We discuss the structures and functions of the two IGF receptors, out line the actions of the six IGFBPs, and summarize and interpret recent studies highlighting essential roles for components of the IGF system in the growth and development of the embryo and fetus, in tissue diff erentiation, in cell survival and proliferation, and in cancer. These results are discussed in the context of new opportunities for understa nding the mechanisms of IGF action in multiple biological processes.