title: The inhibitory effect of cyclic AMP on phosphatidylinositol kinase is not mediated by the cAMP dependent protein kinase.
abstract: Addition of cAMP to cells has been shown to inhibit phosphatidylinositol (PI) metabolism. cAMP has been reported to inhibit an enzyme in this pathway, PI kinase and it has been suggested that this inhibition is due to phosphorylation of PI kinase by the cAMP dependent protein kinase (PKA). In the present study we directly investigated if the inhibitory effect of cAMP was mediated by PKA. In membranes derived from murine hepatocytes we found that cAMP inhibited PI kinase but other adenine derivatives were more potent inhibitors. Moreover, it was found that the effects of the derivatives were unlikely to be due secondarily to the production of cAMP via their interaction with adenosine receptors. Through studies employing an inhibitor of PKA, mutant cells lacking PKA, and addition of purified catalytic subunit of PKA, we found that the inhibitory effect of cAMP was not mediated by PKA. In addition, the inhibitory effect of cAMP and adenosine was retained upon partial purification of PI kinase. Pulse chase experiments affirmed that the inhibitory effect was not due to breakdown of PI but rather to inhibition of its synthesis. We conclude that the inhibitory effect of cAMP and related compounds on PI kinase is not mediated by PKA dependent phosphorylation but rather appears to be a direct effect of these agents.
mesh_terms: D019870:1-Phosphatidylinositol 4-Kinase; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology; D051379:Mice; D010770:Phosphotransferases / Q000037:antagonists & inhibitors*; D011494:Protein Kinases / Q000378:metabolism*
chemical_list: D000242:Cyclic AMP; D010770:Phosphotransferases; D011494:Protein Kinases; D019870:1-Phosphatidylinositol 4-Kinase; D000241:Adenosine