ERK signaling promotes cell motility by inducing the localization of myosin 1E to lamellipodial tips.
ERK signaling promotes cell motility by inducing the localization of myosin 1E to lamellipodial tips.
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DOI：
10.1083/jcb.201503123
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发表时间：
2016-08-15
期刊：
影响因子：
--
通讯作者：
Kohno M
中科院分区：
文献类型：
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作者：
Tanimura S;Hashizume J;Arichika N;Watanabe K;Ohyama K;Takeda K;Kohno M
TAnimura等人的研究。证明SH3P2与肌球蛋白1E(Myo1E)结合并作为胞浆锚定发挥作用。ERK信号依赖的SH3P2的磷酸化导致结合的Myo1E的解离，并随后定位到片状脂膜的末端，在那里它促进细胞运动。细胞外信号调节激酶(ERK)在细胞运动的诱导中起着重要的作用，但这种调控的确切机制仍不清楚。我们最近发现SH3P2是一种细胞运动的负性调节因子，其功能被p90核糖体S6激酶(RSK)介导的ERK下游的磷酸化抑制。我们在这里证明了肌球蛋白1E(Myo1E)是SH3P2的结合伙伴，并且这两种蛋白在胞浆中的相互作用阻止了Myo1E定位于质膜。血清通过RSK诱导SH3P2在Ser202位的磷酸化，导致胞浆中Myo1E从SH3P2中解离，随后Myo1E通过其TH2结构域与F-肌动蛋白结合而定位于片状脂膜末端。Myo1E的这种易位对于片状磷脂的伸展和随后的细胞迁移是必不可少的。因此，ERK信号通路通过调节Myo1E的亚细胞定位来促进细胞运动。
Tanimura et al. demonstrate that SH3P2 binds to and functions as a cytosolic anchor for myosin 1E (Myo1E). ERK signaling–dependent phosphorylation of SH3P2 induces the dissociation of bound Myo1E and its consequent localization to the tips of lamellipodia, where it promotes cell motility. Signaling by extracellular signal–regulated kinase (ERK) plays an essential role in the induction of cell motility, but the precise mechanism underlying such regulation has remained elusive. We recently identified SH3P2 as a negative regulator of cell motility whose function is inhibited by p90 ribosomal S6 kinase (RSK)–mediated phosphorylation downstream of ERK. We here show that myosin 1E (Myo1E) is a binding partner of SH3P2 and that the interaction of the two proteins in the cytosol prevents the localization of Myo1E to the plasma membrane. Serum-induced phosphorylation of SH3P2 at Ser202 by RSK results in dissociation of Myo1E from SH3P2 in the cytosol and the subsequent localization of Myo1E to the tips of lamellipodia mediated by binding of its TH2 domain to F-actin. This translocation of Myo1E is essential for lamellipodium extension and consequent cell migration. The ERK signaling pathway thus promotes cell motility through regulation of the subcellular localization of Myo1E.