Autophosphorylation of a newly identified site of Aurora-B is indispensable for cytokinesis
Autophosphorylation of a newly identified site of Aurora-B is indispensable for cytokinesis
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DOI：
10.1074/jbc.m311128200
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发表时间：
2004-03-26
影响因子：
4.8
通讯作者：
Inagaki, M
中科院分区：
文献类型：
--
作者：
Yasui, Y;Urano, T;Inagaki, M
有丝分裂激酶调节细胞分裂及其检查点，其错误可导致非整倍体或遗传不稳定。其中之一是Aurora- B，这是哺乳动物细胞中期板染色体排列和细胞质分裂所必需的关键激酶。我们在这里报道了人类Aurora- B在体内通过与内部着丝粒蛋白（INCENP）相互作用而在Thr- 232位点磷酸化。Thr- 232的磷酸化是通过自磷酸化机制发生的，这对于Aurora- B激酶的活性是必不可少的。Aurora- B的激活在时空上与其生理底物组蛋白H3和vimentin的位点特异性磷酸化相关。在Aurora- B TA突变体中，Thr- 232被转化为丙氨酸，这种突变体的过表达经常引起细胞多核。这些结果表明，Thr- 232的磷酸化是Aurora- B活化的重要调控机制。
Mitotic kinases regulate cell division and its checkpoints, errors of which can lead to aneuploidy or genetic instability. One of these is Aurora- B, a key kinase that is required for chromosome alignment at the metaphase plate and for cytokinesis in mammalian cells. We report here that human Aurora- B is phosphorylated at Thr- 232 through interaction with the inner centromere protein ( INCENP) in vivo. The phosphorylation of Thr- 232 occurs by means of an autophosphorylation mechanism, which is indispensable for the Aurora- B kinase activity. The activation of Aurora- B spatio- temporally correlated with the site- specific phosphorylation of its physiological substrates, histone H3 and vimentin. Overexpression of the TA mutant of Aurora- B, in which Thr- 232 was changed into alanine, frequently induced multinuclearity in cells. These results indicate that the phosphorylation of Thr- 232 is an essential regulatory mechanism for Aurora- B activation.