Myosin phosphatase-targeting subunit 1 regulates mitosis by antagonizing polo-like kinase 1
Myosin phosphatase-targeting subunit 1 regulates mitosis by antagonizing polo-like kinase 1
复制标题
DOI：
10.1016/j.devcel.2008.02.013
复制
发表时间：
2008-05-01
影响因子：
11.8
通讯作者：
Matsumura, Fumio
中科院分区：
文献类型：
--
作者：
Yamashiro, Shigeko;Yamakita, Yoshihiko;Matsumura, Fumio
肌球蛋白磷酸酶靶向亚基1（MYPT 1）结合蛋白磷酸酶1（PP 1 C）的催化亚基。这种结合被认为将PP 1C靶向包括肌球蛋白11的特异性底物，从而控制细胞收缩性。令人惊讶的是，我们发现，在有丝分裂过程中，哺乳动物MYPT 1结合polo样激酶1（PLK 1）。MYPT 1在有丝分裂期间被脯氨酸定向激酶磷酸化，包括cdc 2，其产生PLK 1的波罗box结构域的结合基序。已知小干扰RNA对PLK 1的消耗导致γ-微管蛋白向中心体的募集丧失，从而阻断中心体成熟并导致有丝分裂停滞。我们发现MYPT 1和PLK 1的编码恢复了中心体的γ-微管蛋白，挽救了有丝分裂停滞。MYPT 1耗竭增加了PLK 1在其激活位点（Thr 210）的体内磷酸化，至少部分解释了通过codeplex的拯救表型。总之，我们的研究结果确定了一个以前未被认识的作用MYPT 1通过拮抗PLK 1调节有丝分裂。
Myosin phosphatase-targeting subunit 1 (MYPT1) binds to the catalytic subunit of protein phosphatase 1 (PP1 C). This binding is believed to target PP1 C to specific substrates including myosin 11, thus controlling cellular contractility. Surprisingly, we found that during mitosis, mammalian MYPT1 binds to polo-like kinase 1 (PLK1). MYPT1 is phosphorylated during mitosis by proline-directed kinases including cdc2, which generates the binding motif for the polo box domain of PLK1. Depletion of PLK1 by small interfering RNAs is known to result in loss of gamma-tubulin recruitment to the centrosomes, blocking centrosome maturation and leading to mitotic arrest. We found that codepletion of MYPT1 and PLK1 reinstates gamma-tubulin at the centrosomes, rescuing the mitotic arrest. MYPT1 depletion increases phosphorylation of PLK1 at its activating site (Thr210) in vivo, explaining, at least in part, the rescue phenotype by codepletion. Taken together, our results identify a previously unrecognized role for MYPT1 in regulating mitosis by antagonizing PLK1.