Regulation of adenylate cyclase by hormones and G-proteins

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.