Protein kinase D is a downstream target of protein kinase Ctheta.
Protein kinase D (PKD/PKCmu immunoprecipitated from either COS-7 cells or Jurkat T lymphocytes transiently transfected with a constitutively active mutant of PKCtheta AE (PKCthetaAE) exhibited a marked increase in basal activity. In contrast, coexpression of constitutively active mutant of PKCzeta does not induce PKD activation in both types of cells. PKCthetaAE does not induce kinase activity in immunocomplexes of PKD kinase-deficient mutants PKDK618N or PKDD733A. PKD activation in response to PKCthetaAE signaling was completely prevented by treatment with the protein kinase C (PKC) inhibitors, GF I or Ro 31-8220, or by mutation of Ser-744 and Ser-748 to Ala in the kinase activation loop of PKD. Our results show that PKD is a downstream target of the theta isoform of PKC in both COS-7 cells and lymphocytes. The regulation of PKD by PKCtheta reveals a new pathway in the signaling network existing between multiple members of the PKC superfamily and PKD.
Yuan
Jingzhen
J
Unit of Signal Transduction and Gastrointestinal Cancer, Department of Medicine, UCLA School of Medicine, Los Angeles, CA 90095, USA.
Bae
David
D
Cantrell
Doreen
D
Nel
Andre E
AE
Rozengurt
Enrique
E
D000409:Alanine / Q000235:genetics; D019943:Amino Acid Substitution; D000818:Animals; D019556:COS Cells; D020134:Catalytic Domain; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D019169:Jurkat Cells; D008301:Maleimides / Q000494:pharmacology; D009154:Mutation; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011233:Precipitin Tests; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000502:physiology*; D000074121:Protein Kinase C-theta; D012694:Serine / Q000235:genetics; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000201:enzymology*; D014162:Transfection
D004791:Enzyme Inhibitors; D007211:Indoles; D007527:Isoenzymes; D008301:Maleimides; D015240:Phorbol 12,13-Dibutyrate; D012694:Serine; C089212:protein kinase D; C076233:PRKCQ protein, human; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta; C070515:bisindolylmaleimide I; D000409:Alanine; C064758:Ro 31-8220