Type-specific stimulation of adenylylcyclase by protein kinase C

• Published in: The Journal of biological chemistry Vol. 268; no. 7; pp. 4604 - 4607
• Main Authors: YOSHIMURA, M, COOPER, D. M. F
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 05.03.1993
• Subjects: adenylate cyclase; Adenylyl Cyclases - genetics; Adenylyl Cyclases - metabolism; Alkaloids - pharmacology; Analytical, structural and metabolic biochemistry; Biological and medical sciences; cell lines; Cells, Cultured; Cyclic AMP - metabolism; DNA; Enzyme Activation; Enzymes and enzyme inhibitors; Fundamental and applied biological sciences. Psychology; Humans; Isoenzymes - metabolism; Lyases; man; Phorbol 12,13-Dibutyrate - pharmacology; protein kinase C; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - metabolism; regulatory; role; Staurosporine; stimulation; Tetradecanoylphorbol Acetate - pharmacology; Transfection; Human; Adenylate cyclase; Signal transduction; Protein kinase C; Calcium; Radiolabelling; Enzyme; Isozyme; Stimulation
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(18)53439-6

Ca(2+)-stimulable (type I), Ca(2+)-insensitive (type II), and Ca(2+)-inhibitable adenylylcyclase (type VI) were transiently expressed in the human embryonic kidney 293 cell line. Phorbol 12,13-dibutyrate (PDBu) increased cAMP synthesis by the Ca(2+)-insensitive type II adenylylcyclase more than 9-fold within 10 min, while the treatment had no effect on the other two types of adenylylcyclases. This stimulatory effect of PDBu on type II activity was dose-dependent and synergistic with the effect of forskolin. Another phorbol ester, phorbol 12-myristate 13-acetate (PMA), had a similar stimulatory effect on type II activity, while its inactive isomer, 4 alpha-phorbol 12-myristate 13-acetate (4 alpha-PMA), had no effect. Staurosporine, a potent protein kinase C (PKC) inhibitor, markedly attenuated the action of PDBu on cAMP synthesis by type II adenylylcyclase. These results are particularly significant in that they indicate that a species of adenylylcyclase that is insensitive to regulation by one arm of the phosphatidylinositide pathway, i.e. Ca2+, nevertheless can be regulated by the other arm, i.e. PKC.