CONFORMATION-DEPENDENT ACTIVATION OF TYPE-II ADENYLYL-CYCLASE BY PROTEIN-KINASE-C

Phorbol ester treatment enhanced the catalytic activity of type II ade nylyl cyclase overexpressed in insect cells. In cells coexpressing typ e II adenylyl cyclase and protein kinase C-alpha, type II adenylyl cyc lase catalytic activity was higher even in the absence of phorbol este r treatment; phorbol ester treatment further and markedly enhanced typ e II adenylyl cyclase catalytic activity. However, this enhancement, e ither by phorbol ester treatment or by coexpression of protein kinase C-alpha, was lost following membrane solubilization with detergents. T his attenuation was unaffected by phosphatase inhibitor or salts. In c ontrast, membrane solubilization did not affect forskolin-stimulated t ype II adenylyl cyclase catalytic activity. Purified type II adenylyl cyclase was stimulated by forskolin and Gs alpha, but not by protein k inase C-alpha. Therefore, a specific mammalian protein kinase C isoenz yme can activate type II adenylyl cyclase, bur the mechanism clearly d iffers from that underlying either Gs alpha- or forskolin-mediated sti mulation. (C) 1997 Wiley-Liss, Inc.