THE INSULIN-LIKE GROWTH-FACTOR-I RECEPTOR - STRUCTURE, LIGAND-BINDINGMECHANISM AND SIGNAL-TRANSDUCTION

The nonclassical binding kinetics of IGF-I and insulin to their respec tive receptors, suggestive of negative cooperativity, can be readily e xplained by our recently proposed novel binding mechanism whereby the bivalent ligand bridges the two receptor alpha-subunits alternatively at opposite sites in a symmetrical receptor structure. The bivalent bi nding mechanism also explains bell-shaped bioactivity curves. The poss ible role of different binding modes versus differences in downstream signaling by insulin and IGF-I in producing specific mitogenic or meta bolic responses is discussed.