Braconi Quintaje S, Church D J, Rebsamen M, Valloton M B, Hemmings B A, Lang U
Division of Endocrinology, University Hospital, Geneva, Switzerland.
Biochem Biophys Res Commun. 1996 Apr 25;221(3):539-47. doi: 10.1006/bbrc.1996.0632.
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.
将培养的新生大鼠心室心肌细胞与100 nM佛波醇12 -肉豆蔻酸酯-13 -乙酸酯（PMA）孵育，5分钟时PP2A活性出现短暂抑制，暴露于PMA 15分钟后该效应逆转。这种失活与PP2A催化亚基磷酸化水平的短暂升高相关（5分钟时为对照水平的193±38%）。在PP2A短暂失活的同时，我们观察到用PMA处理的心肌细胞中42 kDa MAP激酶迅速且可逆的磷酸化（5分钟时为对照水平的474±65%，15分钟时为316±44%）。这种短暂的磷酸化伴随着胞质MAP激酶活性的短暂升高（5分钟时为对照值的209±17%，15分钟时为125±7%）。冈田酸（1 μM）完全阻断了暴露于PMA 5分钟后MAP激酶磷酸化水平和活性的降低。这些数据表明，在心肌细胞中PP2A失活与MAP激酶激活密切相关，表明PP2A在MAP激酶活性调节中起负调节作用。
