Activation of the WAVE complex by coincident signals controls actin assembly.
Activation of the WAVE complex by coincident signals controls actin assembly.
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DOI：
10.1016/j.molcel.2009.10.024
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发表时间：
2009-11-13
期刊：
影响因子：
16
通讯作者：
Kirschner MW
中科院分区：
文献类型：
--
作者：
Lebensohn AM;Kirschner MW
WAVE蛋白通过激活Arp2/3复合体将上游信号与肌动蛋白成核连接起来，是驱动膜突出的调控途径的核心。它们存在于异戊二胺复合物中，其在调节WAVE功能中的作用目前尚不清楚。在这里，我们证明纯化的天然WAVE复合物是碱性无活性的；先前的本构活性报告是体外操作的产物。此外，天然配合物不是由Rac单独激活的。WAVE2复合物的激活需要与丙烯基化的Rac-GTP和酸性磷脂同时相互作用，以及特定的磷酸化状态。这些信号通过诱导复合物的变构变化，而不是通过亚基的简单招募或解离，共同促进膜表面高度协同过程的充分激活。这些结果解释了在细胞运动过程中，WAVE复合体如何整合一致的信号来促进局部肌动蛋白成核。
WAVE proteins link upstream signals to actin nucleation by activating the Arp2/3 complex and are at the core of regulatory pathways driving membrane protrusion. They are found in heteropentameric complexes whose role in regulating WAVE function is presently unclear. Here we demonstrate that purified native WAVE complexes are basally inactive; previous reports of constitutive activity are artifacts of in vitro manipulation. Further, the native complexes are not activated by Rac alone. Activation of the WAVE2 complex requires simultaneous interactions with prenylated Rac-GTP and acidic phospholipids, as well as a specific state of phosphorylation. Together these signals promote full activation in a highly cooperative process on the membrane surface, by inducing an allosteric change in the complex rather than by simple recruitment or by dissociation of the subunits. These results explain how the WAVE complex can integrate coincident signals to promote localized actin nucleation during cell motility.
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影响因子：
4.8
作者：
Kobayashi, K;Kuroda, S;Kaibuchi, K
通讯作者：
Kaibuchi, K
影响因子：
11.4
作者：
Miki, H;Suetsugu, S;Takenawa, T
通讯作者：
Takenawa, T
DOI：
10.1073/pnas.0400628101
发表时间：
2004-03-30
影响因子：
11.1
作者：
Gautreau, A;Ho, HYH;Kirschner, MW
通讯作者：
Kirschner, MW
影响因子：
64.8
作者：
Miki, H;Yamaguchi, H;Takenawa, T
通讯作者：
Takenawa, T
影响因子：
9.2
作者：
Hoeller, Oliver;Kay, Robert R.
通讯作者：
Kay, Robert R.