The Aurora-B-mediated phosphorylation of SHCBP1 regulates cytokinetic furrow ingression
The Aurora-B-mediated phosphorylation of SHCBP1 regulates cytokinetic furrow ingression
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DOI：
10.1242/jcs.124875
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发表时间：
2013-08-01
影响因子：
4
通讯作者：
Senga, Takeshi
中科院分区：
文献类型：
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作者：
Asano, Eri;Hasegawa, Hitoki;Senga, Takeshi
由MgcRacGAP和MKLP 1组成的Centralspindlin是中央纺锤体形成和细胞动力学沟内移所必需的。MgcRacGAP利用其GAP结构域来抑制Rac 1并诱导哺乳动物细胞中的沟内表达。在这份报告中，我们提出了一种新的调节机制，开沟是由磷酸化的SHC SH 2-域结合蛋白1（SHCBP 1），中央spindlin的结合伙伴，极光B（AurB）。AurB在有丝分裂期间磷酸化SHCBP 1的Ser 634。我们产生了一个磷酸化位点突变体，S634 A-SHCBP 1，这是过早招募到中央纺锤体在后期和抑制开沟。体外GAP试验表明，SHCBP 1可以抑制MgcRacGAP介导的Rac 1失活。此外，Rac 1活性的抑制挽救了由S634 A-SHCBP 1表达诱导的犁沟缺陷。因此，AurB磷酸化SHCBP 1，以防止SHCBP 1过早定位到中央纺锤体，并确保MgcRacGAP灭活Rac 1，以促进细胞动力学沟的侵入。
Centralspindlin, which is composed of MgcRacGAP and MKLP1, is essential for central spindle formation and cytokinetic furrow ingression. MgcRacGAP utilizes its GAP domain to inactivate Rac1 and induce furrow ingression in mammalian cells. In this report, we present a novel regulatory mechanism for furrowing that is mediated by the phosphorylation of SHC SH2-domain binding protein 1 (SHCBP1), a binding partner of centralspindlin, by Aurora B (AurB). AurB phosphorylates Ser634 of SHCBP1 during mitosis. We generated a phosphorylation site mutant, S634A-SHCBP1, which was prematurely recruited to the central spindle during anaphase and inhibited furrowing. An in vitro GAP assay demonstrated that SHCBP1 can suppress the MgcRacGAP-mediated inactivation of Rac1. In addition, the inhibition of Rac1 activity rescued the furrowing defect induced by S634A-SHCBP1 expression. Thus, AurB phosphorylates SHCBP1 to prevent the premature localization of SHCBP1 to the central spindle and ensures that MgcRacGAP inactivates Rac1 to promote the ingression of the cytokinetic furrow.