Misshapen-like kinase 1 (MINK1) Is a Novel Component of Striatin-interacting Phosphatase and Kinase (STRIPAK) and Is Required for the Completion of Cytokinesis
Misshapen-like kinase 1 (MINK1) Is a Novel Component of Striatin-interacting Phosphatase and Kinase (STRIPAK) and Is Required for the Completion of Cytokinesis
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DOI：
10.1074/jbc.m112.372342
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发表时间：
2012-07-20
影响因子：
4.8
通讯作者：
Senga, Takeshi
中科院分区：
文献类型：
--
作者：
Hyodo, Toshinori;Ito, Satoko;Senga, Takeshi
胞质分裂由分裂沟的收缩开始，并由连接两个分离的子细胞的细胞间桥的断裂终止。胞质分裂的复杂过程由蛋白激酶和磷酸酶介导的磷酸化和去磷酸化来协调。哺乳动物畸形样激酶1（MINK1）是生殖细胞中心激酶的成员，已知其调节细胞骨架组织和癌基因诱导的细胞衰老。为了寻找胞质分裂的新调节因子，我们使用siRNA文库进行了筛选，发现MINK1对胞质分裂是必需的。时间推移分析显示，MINK1耗尽的细胞能够启动开沟，但破坏。STRN4（Zinedin）是蛋白磷酸酶2A（PP2A）的调节亚基，最近被证明是一种新的蛋白质复合物的组成部分，称为纹状体相互作用磷酸酶和激酶（STRIPAK）。质谱分析表明MINK 1是STRIPAK的一个组分，并且MINK 1直接与STRN 4相互作用。与MINK1耗竭类似，STRN4敲低诱导多核细胞并抑制凋亡的完成。此外，在PP2A的催化和结构亚基存在下，STRN4降低MINK1活性。我们的研究确定了一个新的蛋白激酶和磷酸酶的调节网络，调节完成的分解。
Cytokinesis is initiated by constriction of the cleavage furrow and terminated by abscission of the intercellular bridge that connects two separating daughter cells. The complicated processes of cytokinesis are coordinated by phosphorylation and dephosphorylation mediated by protein kinases and phosphatases. Mammalian Misshapen-like kinase 1 (MINK1) is a member of the germinal center kinases and is known to regulate cytoskeletal organization and oncogene-induced cell senescence. To search for novel regulators of cytokinesis, we performed a screen using a library of siRNAs and found that MINK1 was essential for cytokinesis. Time-lapse analysis revealed that MINK1-depleted cells were able to initiate furrowing but that abscission was disrupted. STRN4 (Zinedin) is a regulatory subunit of protein phosphatase 2A (PP2A) and was recently shown to be a component of a novel protein complex called striatin-interacting phosphatase and kinase (STRIPAK). Mass spectrometry analysis showed that MINK1 was a component of STRIPAK and that MINK1 directly interacted with STRN4. Similar to MINK1 depletion, STRN4-knockdown induced multinucleated cells and inhibited the completion of abscission. In addition, STRN4 reduced MINK1 activity in the presence of catalytic and structural subunits of PP2A. Our study identifies a novel regulatory network of protein kinases and phosphatases that regulate the completion of abscission.