A crucial role in cell spreading for the interaction of Abl PxxP motifs with Crk and Nck adaptors
A crucial role in cell spreading for the interaction of Abl PxxP motifs with Crk and Nck adaptors
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DOI：
10.1242/jcs.031575
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发表时间：
2008-09-15
影响因子：
4
通讯作者：
Mayer, Bruce J.
中科院分区：
文献类型：
--
作者：
Antoku, Susumu;Saksela, Kalle;Mayer, Bruce J.
肌动蛋白结构的动态重组有助于介导细胞与环境的相互作用。Abl非受体酪氨酸激酶可以调节细胞附着过程中的肌动蛋白重排。在这里，我们报告的Abl PxxP基序，结合Src同源3（SH3）域，是必不可少的协调调节的丝状伪足和粘着斑的形成和细胞扩散的动态过程中的附件。通过筛选全面的SH3结构域噬菌体展示文库来鉴定候选Abl PxxP基序结合配偶体。蛋白质过表达、沉默、药理学操作和突变分析的组合表明，Abl的PxxP基序通过两种不同的机制对肌动蛋白组织产生影响，包括抑制Crk信号传导和参与Nck。这些结果揭示了一个以前不受重视的作用Abl PxxP基序在细胞扩散的调节。
The dynamic reorganization of actin structures helps to mediate the interaction of cells with their environment. The Abl nonreceptor tyrosine kinase can modulate actin rearrangement during cell attachment. Here we report that the Abl PxxP motifs, which bind Src homology 3 (SH3) domains, are indispensable for the coordinated regulation of filopodium and focal adhesion formation and cell-spreading dynamics during attachment. Candidate Abl PxxP-motif-binding partners were identified by screening a comprehensive SH3-domain phage-display library. A combination of protein overexpression, silencing, pharmacological manipulation and mutational analysis demonstrated that the PxxP motifs of Abl exert their effects on actin organization by two distinct mechanisms, involving the inhibition of Crk signaling and the engagement of Nck. These results uncover a previously unappreciated role for Abl PxxP motifs in the regulation of cell spreading.