Activation of soluble guanylate cyclase through phosphorylation by protein kinase C in intact PC12 cells.
Soluble guanylate cyclase was found to be phosphorylated by protein kinase C in intact PC12 pheochromocytoma cells. The phosphate incorporation into guanylate cyclase upon addition of phorbol 12-O-myristate 13-acetate (PMA) to PC12 cells in culture coincided with an increased intracellular cGMP level. A strong correlation between phosphate incorporation into guanylate cyclase and increased cGMP level was also observed by time-course and dose-response studies of the PMA effect, as well as when cells were treated with various phorbol esters and diacylglycerols or with various protein kinase C inhibitors. The cAMP system and the presence of extracellular Ca2+ were found not to be involved in guanylate cyclase phosphorylation. The phosphorylation and activation of guanylate cyclase by protein kinase C represent a possible mechanism whereby agonist-stimulation of receptors coupled to phosphoinositide hydrolysis induces cGMP synthesis.
Louis
J C
JC
Unité INSERM U-338, Centre de Neurochimie CNRS, Strasbourg, France.
Revel
M O
MO
Zwiller
J
J
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D006152:Cyclic GMP / Q000096:biosynthesis; D004075:Diglycerides; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000378:metabolism*; D016716:PC12 Cells; D010703:Phorbol Esters; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004075:Diglycerides; D010703:Phorbol Esters; D000242:Cyclic AMP; D011493:Protein Kinase C; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium