Aurora-B and Rho-kinase/ROCK, the two cleavage furrow kinases, independently regulate the progression of cytokinesis: possible existence of a novel cleavage furrow kinase phosphorylates ezrin/radixin/moesin (ERM)
Aurora-B and Rho-kinase/ROCK, the two cleavage furrow kinases, independently regulate the progression of cytokinesis: possible existence of a novel cleavage furrow kinase phosphorylates ezrin/radixin/moesin (ERM)
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DOI：
10.1111/j.1365-2443.2005.00824.x
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发表时间：
2005-02-01
期刊：
影响因子：
2.1
通讯作者：
Inagaki, M
中科院分区：
文献类型：
--
作者：
Yokoyama, T;Goto, H;Inagaki, M
胞质分裂受几种蛋白激酶如Aurora-B和Rho-激酶/ROCK调节。我们已经表明，这两种激酶是卵裂沟（CF）激酶，其在卵裂沟处积累并将几种中间丝（IF）蛋白磷酸化成两个子细胞。据报道，Aurora-B磷酸化MgcRacGAP以在胞质分裂期间功能性地转化为RhoGAP。因此，我们在这里研究Aurora-B和Rho激酶/ROCK在胞质分裂中的关系，通过小干扰RNA（siRNA）技术。Aurora-B耗竭不改变Rho激酶/ROCK的切割沟特异性定位，反之亦然。Aurora-B或Rho激酶/ROCK siRNA处理增加了多核细胞，并且双重消耗的效果是累加的。Aurora-B耗竭诱导丝氨酸72处的波形蛋白的切割沟特异性磷酸化减少，但丝氨酸71处的波形蛋白、丝氨酸19处的肌球蛋白轻链（MLC）和丝氨酸852处的肌球蛋白磷酸酶（MBS）的肌球蛋白结合亚基的磷酸化不减少。相比之下，Rho激酶/ROCK耗竭导致MLC在Ser 19、MBS在Ser 852和波形蛋白在Ser 71的切割沟特异性磷酸化减少，但波形蛋白在Ser 72不减少。在Aurora-B-和/或Rho-激酶/ROCK-耗竭的细胞中，切割沟特异性埃兹蛋白/根蛋白/膜突蛋白（ERM）磷酸化没有改变。此外，C3或毒素B处理并没有废除在细胞分裂沟的ERM磷酸化获得胞质分裂。这些结果表明，Aurora-B和Rho激酶/ROCK调节胞质分裂的进程，而不相互沟通，可能存在一种新的蛋白激酶，磷酸化的ERM在分裂沟。
Cytokinesis is regulated by several protein kinases, such as Aurora-B and Rho-kinase/ROCK. We have indicated that these two kinases are the cleavage furrow (CF) kinases that accumulate at the cleavage furrow and phosphorylate several intermediate filament (IF) proteins into two daughter cells. It has been reported that Aurora-B phosphorylates MgcRacGAP to functionally convert to a RhoGAP during cytokinesis. Therefore, we investigated here the relationship between Aurora-B and Rho-kinase/ROCK in cytokinesis, by using small interfering RNA (siRNA) technique. Aurora-B depletion did not alter the cleavage furrow-specific localization of Rho-kinase/ROCK and vice versa. Treatment of Aurora-B or Rho-kinase/ROCK siRNA increased multinucleate cells, and the effect of double depletion was additive. Aurora-B depletion induced the reduction of cleavage furrow-specific phosphorylation of vimentin at Ser72 but not vimentin at Ser71, myosin light chain (MLC) at Ser19, and myosin binding subunit of myosin phosphatase (MBS) at Ser852. In contrast, Rho-kinase/ROCK depletion led to the reduction of cleavage furrow-specific phosphorylation of MLC at Ser19, MBS at Ser852, and vimentin at Ser71 but not vimentin at Ser72. Cleavage furrow-specific ezrin/radixin/moesin (ERM) phosphorylation was not altered in the Aurora-B- and/or Rho-kinase/ROCK-depleted cells. In addition, C3 or toxin B treatment did not abolish ERM phosphorylation at the cleavage furrow in cells attaining cytokinesis. These results suggest that Aurora-B and Rho-kinase/ROCK regulate the progression of cytokinesis without communicating to each other, and there may exist a novel protein kinase which phosphorylates ERM at the cleavage furrow.