title: Phosphorylation of phospholipase C-gamma by cAMP-dependent protein kinase.
abstract: The mechanism by which cAMP modulates the activity of phosphoinositide-specific phospholipase C (PLC) was studied. Elevation of cAMP inhibited both basal and norepinephrine-stimulated phosphoinositide breakdown in C6Bu1 cells which contain at least three PLC isozymes, PLC-beta, PLC-gamma, and PLC-delta. Treatment of C6Bu1 cells with cAMP-elevating agents (cholera toxin, isobutylmethylxanthine, forskolin, and 8-bromo-cAMP) increased serine phosphate in PLC-gamma, but the phosphate contents in PLC-beta and PLC-delta were not changed. In addition, cAMP-dependent protein kinase selectively phosphorylated purified PLC-gamma among the three isozymes and added a single phosphate at serine. The serine phosphorylation, nevertheless, did not affect the activity of PLC-gamma in vitro. We propose, therefore, that the phosphorylation of PLC-gamma by cAMP-dependent protein kinase alters its interaction with putative modulatory proteins and leads to its inhibition.
authors: Laboratory of Biochemistry, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892.
authors: U H
authors: UH
authors: Kim
authors: J W
authors: JW
authors: Kim
authors: S G
authors: SG
authors: Rhee
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D002460:Cell Line; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D005910:Glioma; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D014407:Tumor Cells, Cultured / Q000201:enzymology; D010738:Type C Phospholipases / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D007527:Isoenzymes; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D002772:Cholera Toxin; D000242:Cyclic AMP; D011494:Protein Kinases; D010738:Type C Phospholipases; D015056:1-Methyl-3-isobutylxanthine