Regulation of Kinetochore Recruitment of Two Essential Mitotic Spindle Checkpoint Proteins by Mps1 Phosphorylation
Regulation of Kinetochore Recruitment of Two Essential Mitotic Spindle Checkpoint Proteins by Mps1 Phosphorylation
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DOI：
10.1091/mbc.e08-03-0324
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发表时间：
2009-01-01
影响因子：
3.3
通讯作者：
Liu, Xuedong
中科院分区：
文献类型：
--
作者：
Xu, Quanbin;Zhu, Songcheng;Liu, Xuedong
MPS1是一种蛋白激酶，在纺锤体检查点信号传导中起重要作用。未附着的动粒或缺乏张力触发了几个关键的纺锤体检查点蛋白向动粒的募集，这延迟了后期的开始，直到重新建立适当的附着或张力。Mps1在纺锤体检查点信号级联的上游起作用，并且Mps1的动粒靶向是随后将Mad1和Mad2募集到动粒所必需的。纺锤体检查点激活后，Mps1或其他检查点蛋白向动粒募集的机制还不完全清楚。在这里，我们表明，磷酸化的Mps1在T12和S15是必需的Mps1招聘动粒。Mps1动粒募集需要其激酶活性和T12和S15的自磷酸化。T12和S15的突变严重损害了其动粒缔合，并显著减少Mad2向动粒的募集。我们的研究强调了Mps1自磷酸化在动粒靶向和纺锤体检查点信号传导中的重要性。
Mps1 is a protein kinase that plays essential roles in spindle checkpoint signaling. Unattached kinetochores or lack of tension triggers recruitment of several key spindle checkpoint proteins to the kinetochore, which delays anaphase onset until proper attachment or tension is reestablished. Mps1 acts upstream in the spindle checkpoint signaling cascade, and kinetochore targeting of Mps1 is required for subsequent recruitment of Mad1 and Mad2 to the kinetochore. The mechanisms that govern recruitment of Mps1 or other checkpoint proteins to the kinetochore upon spindle checkpoint activation are incompletely understood. Here, we demonstrate that phosphorylation of Mps1 at T12 and S15 is required for Mps1 recruitment to the kinetochore. Mps1 kinetochore recruitment requires its kinase activity and autophosphorylation at T12 and S15. Mutation of T12 and S15 severely impairs its kinetochore association and markedly reduces recruitment of Mad2 to the kinetochore. Our studies underscore the importance of Mps1 autophosphorylation in kinetochore targeting and spindle checkpoint signaling.