Signaling-dependent Phosphorylation of Mitotic Centromere-associated Kinesin Regulates Microtubule Depolymerization and Its Centrosomal Localization
Signaling-dependent Phosphorylation of Mitotic Centromere-associated Kinesin Regulates Microtubule Depolymerization and Its Centrosomal Localization
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DOI：
10.1074/jbc.m112.399576
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发表时间：
2012-11-23
影响因子：
4.8
通讯作者：
Kumar, Rakesh
中科院分区：
文献类型：
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作者：
Pakala, Suresh B.;Nair, Vasudha S.;Kumar, Rakesh
尽管p21激活的激酶1(PAK1)和微管(MT)的动力学调控着许多基本过程，包括细胞骨架重塑、定向运动和有丝分裂功能，但PAK1信号在调节MT去稳定蛋白有丝分裂着丝粒相关蛋白(MCAK)功能中的意义尚不清楚。在这里，我们发现MCAK是PAK1的同源底物，其中PAK1在体内和体外都将丝氨酸192和111上的MCAK磷酸化。此外，我们还发现，在哺乳动物细胞中，丝氨酸192和111上MCAK的PAK1磷酸化分别优先调节其微管解聚活性和中心体的定位。
Although p21-activated kinase 1 (PAK1) and microtubule (MT) dynamics regulate numerous fundamental processes including cytoskeleton remodeling, directional motility, and mitotic functions, the significance of PAK1 signaling in regulating the functions of MT-destabilizing protein mitotic centromere-associated kinesin (MCAK) remains unknown. Here we found that MCAK is a cognate substrate of PAK1 wherein PAK1 phosphorylates MCAK on serines 192 and 111 both in vivo and in vitro. Furthermore, we found that PAK1 phosphorylation of MCAK on serines 192 and 111 preferentially regulates its microtubule depolymerization activity and localization to centrosomes, respectively, in the mammalian cells.