c-Abl interacts with the WAVE2 signaling complex to induce membrane ruffling and cell spreading
c-Abl interacts with the WAVE2 signaling complex to induce membrane ruffling and cell spreading
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DOI：
10.1074/jbc.m602389200
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发表时间：
2006-10-20
影响因子：
4.8
通讯作者：
Yuan, Zhi-Min
中科院分区：
文献类型：
--
作者：
Stuart, Jeremy R.;Gonzalez, Francis H.;Yuan, Zhi-Min
Wiskott-Aldrich综合征相关蛋白WAVE 2促进Rho-GTdR激活下游Arp 2/3依赖性肌动蛋白聚合。Abelson相互作用蛋白-1（Abi-1）形成WAVE 2复合物的核心，并且是适当刺激WAVE 2活性所必需的。在这里，我们已经表明，β-酪氨酸激酶与WAVE 2复合物的相互作用和Abl激酶活性促进Abl和WAVE 2复合物成员之间的相互作用。我们已经表征了Abl和WAVE 2复合物的成员之间的各种相互作用，并揭示了Abi-1促进Abl和WAVE 2成员之间的相互作用。我们已经证明，WAVE 2的依赖性磷酸化是其在体内活化所必需的，这通过以下发现来强调，即在Abl/Arg（-/-）细胞中WAVE 2表达的RNA干扰对膜皱褶的量没有累加效应。此外，Abl使酪氨酸150上的WAVE 2磷酸化，并且与用野生型WAVE 2拯救的细胞不同，用Y150 F突变体拯救的WAVE 2缺陷细胞不能重新获得它们的起皱和形成微刺的能力。总之，这些数据表明，c-Abl通过酪氨酸磷酸化激活WAVE 2，以促进体内肌动蛋白重塑，并且Abi-1形成了这两个因子之间的关键联系。
The Wiskott-Aldrich syndrome-related protein WAVE2 promotes Arp2/3-dependent actin polymerization downstream of Rho-GTPase activation. The Abelson-interacting protein-1 (Abi-1) forms the core of the WAVE2 complex and is necessary for proper stimulation of WAVE2 activity. Here we have shown that the Abl-tyrosine kinase interacts with the WAVE2 complex and that Abl kinase activity facilitates interaction between Abl and WAVE2 complex members. We have characterized various interactions between Abl and members of the WAVE2 complex and revealed that Abi-1 promotes interaction between Abl and WAVE2 members. We have demonstrated that Abl-dependent phosphorylation of WAVE2 is necessary for its activation in vivo, which is highlighted by the findings that RNA interference of WAVE2 expression in Abl/Arg(-/-) cells has no additive effect on the amount of membrane ruffling. Furthermore, Abl phosphorylates WAVE2 on tyrosine 150, and WAVE2-deficient cells rescued with a Y150F mutant fail to regain their ability to ruffle and form microspikes, unlike cells rescued with wild-type WAVE2. Together, these data show that c-Abl activates WAVE2 via tyrosine phosphorylation to promote actin remodeling in vivo and that Abi-1 forms the crucial link between these two factors.