PREL1 provides a link from Ras signalling to the actin cytoskeleton via Ena/VASP proteins
PREL1 provides a link from Ras signalling to the actin cytoskeleton via Ena/VASP proteins
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DOI：
10.1016/j.febslet.2004.10.110
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发表时间：
2005-01-17
期刊：
影响因子：
3.5
通讯作者：
Stradal, TEB
中科院分区：
文献类型：
--
作者：
Jenzora, A;Behrendt, B;Stradal, TEB
Ena/VASP家族蛋白是细胞迁移的重要调节剂，并定位于粘着斑、应力纤维以及板状伪足和丝状伪足的尖端。富含脯氨酸的蛋白质如黏着斑蛋白和zyxin是公认的相互作用伴侣，其通过其EVH 1结构域介导Ena/VASP募集至粘着斑和应力纤维。然而，目前还不清楚，哪些结合伙伴Ena/VASP蛋白可能在板状伪足尖端，以及它们的招聘这些细胞突起的调节。在这里，我们报告了一种新的蛋白质的鉴定与线虫的EVH 1 -10蛋白，我们称之为PRELI（脯氨酸丰富EVH 1配体）的高度相似性。PRELI是一种74 kDa的蛋白质，与信号转导衔接子的Grb 7家族具有同源性。我们表明，PRELI直接结合到Ena/VASP蛋白和co-localizes与他们在板状伪足的提示，并在局灶性粘连响应Ras激活。此外，PRELI以磷酸肌醇依赖性方式直接结合活化的Ras。因此，我们的数据指出PRELI是细胞迁移和扩散过程中Ras信号传导和通过Ena/VASP蛋白的细胞骨架重塑之间的第一个直接联系。(C)2004年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
Ena/VASP family proteins are important modulators of cell migration and localize to focal adhesions, stress fibres and the very tips of lamellipodia and filopodia. Proline-rich proteins like vinculin and zyxin are well established interaction partners, which mediate Ena/VASP-recruitment via their EVH1-domains to focal adhesions and stress fibres. However, it is still unclear, which binding partners Ena/VASP proteins may have at lamellipodia tips and how their recruitment to these cellular protrusions is regulated. Here, we report the identification of a novel protein with high similarity to the C elegans MIG-10 protein, which we termed PRELI (Proline Rich EVH1 Ligand). PRELI is a 74 kDa protein and shares homology with the Grb7-family of signalling adaptors. We show that PRELI directly binds to Ena/VASP proteins and co-localizes with them at lamellipodia tips and at focal adhesions in response to Ras activation. Moreover, PRELI directly binds to activated Ras in a phosphoinositide-dependent manner. Thus, our data pinpoint PRELI as the first direct link between Ras signalling and cytoskeletal remodelling via Ena/VASP proteins during cell migration and spreading. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.