OKADAIC ACID, A POTENT INHIBITOR OF TYPE-1 AND TYPE-2A PROTEIN PHOSPHATASES, ACTIVATES CDC2/H1 KINASE AND TRANSIENTLY INDUCES A PREMATURE MITOSIS-LIKE STATE IN BHK-21-CELLS
OKADAIC ACID, A POTENT INHIBITOR OF TYPE-1 AND TYPE-2A PROTEIN PHOSPHATASES, ACTIVATES CDC2/H1 KINASE AND TRANSIENTLY INDUCES A PREMATURE MITOSIS-LIKE STATE IN BHK-21-CELLS
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DOI：
10.1002/j.1460-2075.1990.tb07882.x
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发表时间：
1990-12-01
期刊：
影响因子：
11.4
通讯作者：
NISHIMOTO, T
中科院分区：
文献类型：
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作者：
YAMASHITA, K;YASUDA, H;NISHIMOTO, T
当同步化于早期S期的BHK 21细胞暴露于蛋白磷酸酶1和2A的抑制剂冈田酸（OA）时，诱导了有丝分裂特异性事件，如染色体过早凝聚、MPM-2抗原的产生、核纤层蛋白的分散和有丝分裂星形细胞的出现，然后在进一步孵育时消失。 甚至在放线菌酮存在下也发生这些有丝分裂特异性事件。 在1小时内暴露于OA，cdc 2/组蛋白H1激酶活性上升10倍，与未经处理的对照组相比，但返回到控制水平后，进一步孵育。 使用针对p34 cdc 2或细胞周期蛋白B的抗体，发现与细胞周期蛋白B复合的p34 cdc 2在OA处理后伴随着cdc 2激酶的活化而去磷酸化，并且细胞周期蛋白B随后伴随着cdc 2激酶活性的降低而降解，如在正常有丝分裂中一样。 与此相反，当细胞在G1期与OA处理没有增加cdc 2激酶活性观察。 此外，当用OA处理诺考达唑诱导的假中期细胞时，cdc 2激酶被灭活。 这些结果表明，OA敏感性蛋白磷酸酶控制p34 cdc 2激酶的激活和失活。
When BHK21 cells synchronized in early S phase were exposed to okadaic acid (OA), an inhibitor of protein phosphatases 1 and 2A, mitosis specific events such as premature chromosome condensation, the productions of MPM-2 antigens, dispersion of nuclear lamins and the appearance of mitotic asters were induced, and then disappeared upon further incubation. These mitosis specific events occurred even in the presence of cycloheximide. Within 1 h of exposure to OA, cdc2/histone H1 kinase activity rose 10-fold compared with untreated controls, but returned to the control level upon further incubation. Using antibodies against either p34cdc2 or cyclin B it was found that p34cdc2 complexed with cyclin B was dephosphorylated after OA treatment concomitant with the activation of cdc2 kinase, and that cyclin B was subsequently degraded concomitant with a decrease in cdc2 kinase activity, as in normal mitosis. In contrast, when cells in G1 phase were treated with OA no increase in cdc2 kinase activity was observed. Moreover when cells in pseudo-metaphase induced by nocodazole were treated with OA, cdc2 kinase was inactivated. These results suggest that OA sensitive protein phosphatases control both the activation and inactivation of the p34cdc2 kinase.