Activation of soluble guanylate cyclase through phosphorylation by protein kinase C in intact PC12 cells

Biochim Biophys Acta. 1993 Jun 30;1177(3):299-306. doi: 10.1016/0167-4889(93)90126-a.

Abstract

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.

MeSH terms

  • Animals
  • Calcium / pharmacology
  • Cyclic AMP / biosynthesis
  • Cyclic GMP / biosynthesis
  • Diglycerides
  • Enzyme Activation
  • Guanylate Cyclase / metabolism*
  • PC12 Cells
  • Phorbol Esters
  • Phosphorylation
  • Protein Kinase C / metabolism*
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Diglycerides
  • Phorbol Esters
  • Cyclic AMP
  • Protein Kinase C
  • Guanylate Cyclase
  • Cyclic GMP
  • Tetradecanoylphorbol Acetate
  • Calcium