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Role of protein phosphatase 2A in the regulation of mitogen-activated protein kinase activity in ventricular cardiomyocytes

Church, Dennis J.
Hemmings, B A.
Published in Biochemical and Biophysical Research Communications. 1996, vol. 221, no. 3, p. 539-47
Abstract Incubation of cultured, neonatal rat ventricular cardiomyocytes with 100 nM phorbol 12-myristate-13-acetate (PMA) induced a transient suppression of PP2A activity at 5 min, an effect that was reversed after 15 min of exposure to PMA. This inactivation was correlated with a transient increase in the phosphorylation level of the catalytic subunit of PP2A (193 +/- 38% of control levels at 5 min). Simultaneously to the transient inactivation of PP2A, we observed a rapid and reversible phosphorylation of 42-kDa MAP kinase (474 +/- 65% of control levels at 5 min, and 316 +/- 44% at 15 min) in cardiomyocytes treated with PMA. This transient phosphorylation was accompanied by a transient increase in cytosolic MAP kinase activity (209 +/- 17% of control values at 5 min and 125 +/- 7% at 15 min). Okadaic acid (1 microM ) completely blocked the decrease in the phosphorylation level and activity of MAP kinase occurring after 5 min of exposure to PMA. These data demonstrate that PP2A inactivation and MAP kinase activation are very strongly correlated in cardiomyocytes, indicating that PP2A plays a negative modulatory role in the regulation of MAP kinase activity.
Keywords AnimalsCalcium-Calmodulin-Dependent Protein Kinases/metabolismCells, CulturedEnzyme ActivationEthers, Cyclic/pharmacologyHeart Ventricles/cytology/enzymologyMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Mitogen-Activated Protein KinasesOkadaic AcidPhosphoprotein Phosphatases/antagonists & inhibitors/metabolismPhosphorylationProtein Kinase C/metabolismProtein Phosphatase 2Protein-Tyrosine Kinases/metabolismRatsRats, WistarTetradecanoylphorbol Acetate/pharmacology
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PMID: 8629997
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