Role of type 1 and type 2A phosphatases in signal transduction of platelet-activating-factor-stimulated rabbit platelets.
Role of type 1 and type 2A phosphatases in signal transduction of platelet-activating-factor-stimulated rabbit platelets.
复制标题
1 型和 2A 型磷酸酶在血小板激活因子刺激的兔血小板信号转导中的作用。
作者：
C. Murphy;J. Westwick
Calyculin A是1型（PP 1）和2A型（PP 2A）磷酸酶的有效抑制剂，已被用于研究内源性激活的PP 1/PP 2A在血小板活化因子（PAF）刺激的血小板的信号转导途径中的作用。Calyculin A单独引起未刺激血小板中蛋白磷酸化的增加，检测到一些新的磷酸化蛋白，而在PAF刺激的血小板中，蛋白激酶C和肌球蛋白轻链激酶的主要底物磷酸化不再是短暂的，但磷酸化是持续的。PP 1/PP 2A似乎在Ca 2+稳态中起作用，因为PP 1/PP 2A的抑制导致PAF刺激的血小板中Ca 2+动员和Ca 2+通过质膜内流的抑制。Calyculin A对Ca 2+动员的影响与观察到的信号分子Ins（1，4，5）P3的产生抑制相关。释放反应（这是一个Ca（2+）依赖性事件）也被calyculin A抑制。结果进行了讨论有关的蛋白激酶C在介导的事件，导致观察到的影响与calyculin A的可能作用。
Calyculin A, the potent inhibitor of type 1 (PP1) and type 2A (PP2A) phosphatases, has been employed in order to investigate the role of endogenously activated PP1/PP2A in the signal-transduction pathway of platelet-activating-factor (PAF)-stimulated platelets. Calyculin A alone caused an increase in protein phosphorylation in unstimulated platelets, with the detection of a number of newly phosphorylated proteins, whereas in PAF-stimulated platelets phosphorylation of the major substrates of protein kinase C and myosin light-chain kinase were no longer transient, but phosphorylation was sustained. PP1/PP2A appear to play a role in Ca2+ homoeostasis, as inhibition of PP1/PP2A caused an inhibition of Ca2+ mobilization and Ca2+ influx through the plasma membrane in PAF-stimulated platelets. The effect of calyculin A on Ca2+ mobilization correlated with the observed inhibition of the production of the signal molecule Ins(1,4,5)P3. The release reaction (which is a Ca(2+)-dependent event) was also inhibited by calyculin A. The results are discussed in relation to the possible role of protein kinase C in mediating the events leading to the effects observed with calyculin A.