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 ki nase C in intact PC12 pheochromocytoma cells. The phosphate incorporat ion into guanylate cyclase upon addition of phorbol 12-0-myristate 13- acetate (PMA) to PC12 cells in culture coincided with an increased int racellular cGMP level. A strong correlation between phosphate incorpor ation into guanylate cyclase and increased cGMP level was also observe d by time-course and dose-response studies of the PMA effect, as well as when cells were treated with various phorbol esters and diacylglyce rols or with various protein kinase C inhibitors. The cAMP system and the presence of extracellular Ca2+ were found not to be involved in gu anylate 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 h ydrolysis induces cGMP synthesis.