The M Phase Kinase Greatwall (Gwl) Promotes Inactivation of PP2A/B55δ, a Phosphatase Directed Against CDK Phosphosites
The M Phase Kinase Greatwall (Gwl) Promotes Inactivation of PP2A/B55δ, a Phosphatase Directed Against CDK Phosphosites
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DOI：
10.1091/mbc.e09-07-0643
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发表时间：
2009-11-15
影响因子：
3.3
通讯作者：
Goldberg, Michael L.
中科院分区：
文献类型：
--
作者：
Castilho, Priscila V.;Williams, Byron C.;Goldberg, Michael L.
我们以前已经表明，长城激酶（Gwl）是必需的M期进入和维护非洲爪蟾卵提取物。在这里，我们证明了Gwl在一种新的生物化学途径中起着至关重要的作用，该途径特别是在M期期间使针对细胞周期蛋白依赖性激酶（CDK）催化的磷酸化的“抗有丝分裂”磷酸酶失活。这种磷酸酶活性的主要成分是含有B55 δ调节亚基的异源三聚体PP 2A。Gwl在M期期间被Cdk 1/细胞周期蛋白B（MPF）激活，但是一旦激活，Gwl促进PP 2 A/B55 δ抑制，而不进一步需要MPF。在不存在Gwl的情况下，PP 2A/B55 δ即使在MPF水平高时也保持活性。PP 2A/B55 δ的去除校正了Gwl耗尽的提取物进入M期的能力。这些发现支持以下假设：M期不仅需要高水平的MPF功能，而且还需要通过Gwl依赖性机制抑制磷酸酶，否则磷酸酶将去除MPF驱动的磷酸化。
We have previously shown that Greatwall kinase (Gwl) is required for M phase entry and maintenance in Xenopus egg extracts. Here, we demonstrate that Gwl plays a crucial role in a novel biochemical pathway that inactivates, specifically during M phase, "antimitotic" phosphatases directed against phosphorylations catalyzed by cyclin-dependent kinases (CDKs). A major component of this phosphatase activity is heterotrimeric PP2A containing the B55 delta regulatory subunit. Gwl is activated during M phase by Cdk1/cyclin B (MPF), but once activated, Gwl promotes PP2A/B55 delta inhibition with no further requirement for MPF. In the absence of Gwl, PP2A/B55 delta remains active even when MPF levels are high. The removal of PP2A/B55 delta corrects the inability of Gwl-depleted extracts to enter M phase. These findings support the hypothesis that M phase requires not only high levels of MPF function, but also the suppression, through a Gwl-dependent mechanism, of phosphatase(s) that would otherwise remove MPF-driven phosphorylations.