Dock4 forms a complex with SH3YL1 and regulates cancer cell migration
Dock4 forms a complex with SH3YL1 and regulates cancer cell migration
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DOI：
10.1016/j.cellsig.2014.01.027
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发表时间：
2014-05-01
影响因子：
4.8
通讯作者：
Katoh, Hironori
中科院分区：
文献类型：
--
作者：
Kobayashi, Masakazu;Harada, Kohei;Katoh, Hironori
Dock 4是Dock 180蛋白家族的成员，其通过激活Rac介导癌细胞迁移。然而，Dock 4的调控机制仍不清楚。在这项研究中，我们表明，在MDA-MB-231乳腺癌细胞中，Dock 4的C-末端富含脯氨酸的区域对于Dock 4介导的细胞迁移促进是必不可少的。我们发现磷酸肌醇结合蛋白SH 3 YL 1与Dock 4的C-末端富含脯氨酸的区域相互作用。SH 3 YL 1与Dock 4的相互作用促进Dock 4介导的Rac 1活化和细胞迁移。磷酸肌醇结合结构域的突变破坏了SH 3 YL 1促进Dock 4介导的细胞迁移的能力。此外，MDA-MB-231细胞中SH 3 YL 1的耗竭抑制了细胞迁移。综上所述，这些结果为Dock 4和SH 3 YL 1之间通过调节Rac 1活性促进癌细胞迁移的新型且功能重要的相互作用提供了证据。(C)2014爱思唯尔公司All rights reserved.
Dock4 is a member of the Dock180 family of proteins that mediates cancer cell migration through activation of Rac. However, the regulatory mechanism of Dock4 remains unclear. In this study, we show that the C-terminal praline-rich region of Dock4 is essential for the Dock4 mediated promotion of cell migration in MDA-MB-231 breast cancer cells. We found that a phosphoinositide-binding protein SH3YL1 interacted with the C-terminal praline-rich region of Dock4. Interaction of SH3YL1 with Dock4 promoted Dock4-mediated Rac1 activation and cell migration. Mutations in the phosphoinositide-binding domain disrupted the ability of SH3YL1 to promote Dock4-mediated cell migration. In addition, depletion of SH3YL1 in MDA-MB-231 cells suppressed cell migration. Taken together, these results provide evidence for a novel and functionally important interaction between Dock4 and SH3YL1 to promote cancer cell migration by regulating Rac1 activity. (C) 2014 Elsevier Inc. All rights reserved.