Non-catalytic signaling by pseudokinase ILK for regulating cell adhesion.
Non-catalytic signaling by pseudokinase ILK for regulating cell adhesion.
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DOI：
10.1038/s41467-018-06906-7
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发表时间：
2018-10-26
影响因子：
16.6
通讯作者：
Qin J
中科院分区：
文献类型：
--
作者：
Vaynberg J;Fukuda K;Lu F;Bialkowska K;Chen Y;Plow EF;Qin J
含整合素的复合物（粘着斑，FA）和肌动蛋白丝之间的动态通信是调节细胞粘附的关键。假激酶ILK在这一过程中起着关键作用，但潜在的机制仍然非常难以捉摸。在这里，我们表明，通过招募FA适配器PINCH和Parvin到异源三聚体复合物（IPP），ILK触发F-肌动蛋白丝成束-一个已知的过程，产生力/机械信号，以促进细胞骨架重组和动态细胞粘附。结构，生化和功能分析表明，F-肌动蛋白捆绑是精心策划的两个以前未被识别的WASP同源性-2肌动蛋白结合基序在IPP，一个来自PINCH和其他从Parvin。引人注目的是，这一过程也是敏感的镁ATP结合的假活性位点的ILK和其失调严重损害应力纤维的形成，细胞的蔓延，和迁移。这些数据确定了ILK的关键机制，突出了其作为假激酶抑制非催化信号和调节细胞粘附的独特性。假激酶ILK是黏着斑复合物和F-肌动蛋白丝之间的动态通信所必需的。在这里，作者表明ILK通过与PINCH和Parvin复合来调节这种通信，从而通过PINCH和Parvin中先前未识别的肌动蛋白结合基序触发F-肌动蛋白丝成束。
Dynamic communication between integrin-containing complexes (focal adhesions, FAs) and actin filaments is critical for regulating cell adhesion. Pseudokinase ILK plays a key role in this process but the underlying mechanism remains highly elusive. Here we show that by recruiting FA adaptors PINCH and Parvin into a heterotrimeric complex (IPP), ILK triggers F-actin filament bundling – a process known to generate force/mechanical signal to promote cytoskeleton reassembly and dynamic cell adhesion. Structural, biochemical, and functional analyses revealed that the F-actin bundling is orchestrated by two previously unrecognized WASP-Homology-2 actin binding motifs within IPP, one from PINCH and the other from Parvin. Strikingly, this process is also sensitized to Mg-ATP bound to the pseudoactive site of ILK and its dysregulation severely impairs stress fibers formation, cell spreading, and migration. These data identify a crucial mechanism for ILK, highlighting its uniqueness as a pseudokinase to transduce non-catalytic signal and regulate cell adhesion. Pseudokinase ILK is essential for dynamic communication between focal adhesion complexes and F-actin filaments. Here, the authors show that ILK regulates such communication by complexing with PINCH and Parvin to trigger F-actin filament bundling through previously unrecognized actin binding motifs in PINCH and Parvin
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影响因子：
21.3
作者：
Case LB;Waterman CM
通讯作者：
Waterman CM
ILK的伪活性位点对于它与α-Parvin的结合和与局灶性粘连的定位至关重要。
影响因子：
16
作者：
Fukuda, Koichi;Gupta, Sudhiranjan;Chen, Ka;Wu, Chuanyue;Qin, Jun
通讯作者：
Qin, Jun
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
4.1
作者：
Liang, Xiquan;Potter, Jason;Chesnut, Jonathan D.
通讯作者：
Chesnut, Jonathan D.
DOI：
10.1073/pnas.0811415106
发表时间：
2008-12-30
影响因子：
11.1
作者：
Chiswell, Brian P.;Zhang, Rong;Calderwood, David A.
通讯作者：
Calderwood, David A.