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Functional inhibition of protein kinase C-mediated effects in myocardial tissue is due to the phosphatase 2A

Church, Dennis J.
Published in Biochemical Journal. 1992, vol. 286 (Pt 3), p. 851-855
Abstract An endogenous protein which inhibits protein kinase C (PKC)-mediated effects has been detected in rat heart ventricular tissue. This functional PKC-inhibitory activity was completely abolished by okadaic acid, making it possible to measure PKC activity in non-purified cell fractions. This suggests that the PKC-inhibitory activity is a type 1 or 2A serine/threonine phosphatase. Confirming this, membrane and cytosolic PKC-inhibitory preparations were found to contain phosphatase activity which was suppressed by okadaic acid, exhibiting an IC50 (concn. required for 50% inhibition) of 1.5-2 nM. Furthermore, okadaic acid stimulated prostacyclin production in rat cardiomyocytes and aortic smooth-muscle cells and, like the PKC activator phorbol 12-myristate 13-acetate, it augmented the prostacyclin formation induced by the Ca2+ ionophore A23187. Our results strongly suggest that the endogenous PKC 'inhibitor' is the cellular phosphatase 2A, which plays an important role in regulating the phosphorylation level of PKC target proteins.
Keywords AnimalsCells, CulturedChromatography, DEAE-CelluloseEpoprostenol/biosynthesisEthers, Cyclic/pharmacologyFemaleMuscle, Smooth, Vascular/cytology/metabolismMyocardium/cytology/metabolismOkadaic AcidPhosphoprotein Phosphatases/antagonists & inhibitors/metabolismProtein Kinase C/antagonists & inhibitorsProtein Phosphatase 2RatsRats, Wistar
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PMID: 1329718
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