Two Operational Modes of Transmembrane Migration of Cyclic Gmp Signal Pathway

Abstract

The transformation of a normal cell into a terminal stage of malignancy is a multiple-step biological process in which the initial signal appears to activate a protooncogene into an active oncogene. In this activation process growth factors, including catecholamines and polypeptide hormones, play an important role in the oncogene expression. The mechanisms by which the extracellular signals, such as those of the growth factors, are translated into biological responses is therefore an important problem in both regulatory and cancer biology. There are at present three recognized signal pathways -- cyclic AMP, phosphatidylinositol, and cyclic GMP -- for the propagation of these receptor-mediated events. In my presentation I will address the most recent developments on the nature and the mechanisms of the generation and regulation of transmembrane migration of receptor-mediated cyclic GMP signals. There appear to be at least two very different (direct and indirect) modes of operation of this signal pathway, suggesting the existence of at least two different types of receptor-coupled guanylate cyclases. To date, only one such guanylate cyclase (ANF-dependent) has been identified, which appears to be bifunctional; it is both an ANF receptor and a guanylate cyclase. But evidence strongly suggests the existence of another type of guanylate cyclase that is indirectly coupled to the guanylate cyclase. Both modes of cyclic GMP operational systems at the membrane level appear to be down regulated by protein kinase C, representing a close interaction of the two major cyclic GMP and protein kinase C signal pathways in the generation and regulation of cyclic GMP signals.