ROLE OF THE TIME FACTOR IN SIGNALING SPECIFICITY - APPLICATION TO MITOGENIC AND METABOLIC SIGNALING BY THE INSULIN AND INSULIN-LIKE GROWTH-FACTOR-I RECEPTOR TYROSINE KINASES

The signal transduction pathways activated by hormones, growth factors , and cytokines show an extraordinary degree of cross-talk and redunda ncy. This review addresses the question of how the specificity conferr ed at the binding step is maintained through the signaling network des pite the convergence of multiple signals on common efferent pathways s uch as mitogen-activated protein (MAP) kinase. The mechanism of recept or activation by ligand induced dimerization provides a signaling devi ce with both a switch and a timer. The role of the time factor, ie, of signaling kinetics, as a determinant of selectivity is discussed with emphasis on the receptor tyrosine kinases and cytokine receptors, and especially mitogenic versus metabolic signaling by insulin and insuli n-like growth factor-I (IGF-I). Copyright (C) 1995 by W.B. Saunders Co mpany.