Regulation of adenylate cyclase by hormones and G‐proteins

Abstract

Over the past few years, it has become apparent that a large number of transmembrane signaling systems operate through heterotrimeric G‐proteins ([1] Gilman, A.G. (1984) Cell 36, 577‐579; [2] Baker, P.F. (1986) Nature 320, 395). Adenylate cyclase is regulated by stimulatory hormones through G_s(α_sβγ) and inhibitory hormones through G_i(α_iβγ) ([2]; Katada, T. et al. (1984) J. Biol. Chem. 259, 3586‐3595), whereas the breakdown of phosphatidylinositol bisphosphate (PIP₂) to inositol trisphosphate (IP₃) and diacylglycerol (DG) by phospholipase C is probably also mediated by a heterotrimeric G‐protein (G_o or G_i) [1,2]. Similarly, the activation of cGMP phosphodiesterase by light‐activated rhodopsin is mediated through the heterotrimeric G‐protein transducin (Stryer, L. (1986) Rev. Neurosci. 9, 89‐119). Other transmembrane signaling systems may also be found to involve G‐proteins similar to those already recognized. Because of the emerging universality of G‐proteins as transducers of receptor‐triggered signals, it may be useful to evaluate the current models prevailing in the adenylate cyclase field, as these models seem to guide our way in evaluating the role of G‐proteins in transmembrane signaling, in general.