ROLE OF PROTEIN PHOSPHATASE 2A IN THE REGULATION OF MITOGEN-ACTIVATEDPROTEIN-KINASE ACTIVITY IN VENTRICULAR CARDIOMYOCYTES

Incubation of cultured, neonatal rat ventricular cardiomyocytes with 1 00 nM phorbol 12-myristate-13-acetate (PMA) induced a transient suppre ssion of PP2A activity at 5 min, an effect that was reversed after 15 min of exposure to PMA, This inactivation was correlated with a transi ent increase in the phosphorylation level of the catalytic subunit of PP2A (193 +/- 38% of control levels at 5 min). Simultaneously to the t ransient inactivation of PP2A, we observed a rapid and reversible phos phorylation of 42-kDa MAP kinase (474 +/- 65% of control levels at 5 m in, and 316 +/- 44% at 15 min) in cardiomyocytes treated with PMA. Thi s 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 mu M) completely blocked t he decrease in the phosphorylation level and activity of MAP kinase oc curring after 5 min of exposure to PMA. These data demonstrate that PP 2A inactivation and MAP kinase activation are very strongly correlated in cardiomyocytes, indicating that PP2A plays a negative modulatory r ole in the regulation of MAP kinase activity. (C) 1996 Academic Press, Inc.