Downregulation of protein kinase C-gamma is independent of a functional kinase domain.
Prolonged activation of protein kinase C (PKC) types alpha and beta by tumor-promoting phorbol esters leads to desensitization of the phorbol ester response, downregulation of protein kinase C activity and depletion of the protein kinase C polypeptide. When the gamma isoenzyme of PKC is transiently expressed in COS-1 cells and exposed to phorbol esters, PKC-Gamma is downregulated in COS cells although these cells do not normally express this subtype. A point mutation in the putative ATP-binding site (Lys-380----Met-380) of the protein kinase C gamma isoenzyme which results in a kinase-deficient enzyme does not interfere with this downregulation. Our results suggest that autophosphorylation or constitutive signalling through the protein kinase C-gamma kinase domain is not a prerequisite for downregulation of PKC activity.
Freisewinkel
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Max-Delbrück-Labor in der Max-Planck-Gesellschaft, Köln, Germany.
Riethmacher
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Stabel
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D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D002478:Cells, Cultured; D015536:Down-Regulation; D004789:Enzyme Activation / Q000187:drug effects; D007527:Isoenzymes / Q000378:metabolism; D008239:Lysine / Q000235:genetics; D008715:Methionine / Q000235:genetics; D009154:Mutation; D010703:Phorbol Esters / Q000494:pharmacology; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D011493:Protein Kinase C / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
D007527:Isoenzymes; D010703:Phorbol Esters; D000255:Adenosine Triphosphate; D008715:Methionine; D011493:Protein Kinase C; D008239:Lysine