Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck
Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck
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DOI：
10.1038/nature00859
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发表时间：
2002-08-15
期刊：
影响因子：
64.8
通讯作者：
Kirschner, MW
中科院分区：
文献类型：
--
作者：
Eden, S;Rohatgi, R;Kirschner, MW
RAC信号到肌动蛋白的通路被认为是由蛋白SCAR/WAVE(Wiskott-Aldrich综合征蛋白)-Verprolin家族同源蛋白(WASP)介导的-在细胞运动中起着主要作用。在类似的途径中，Cdc42与相关蛋白N-WASP的直接相互作用刺激肌动蛋白聚合(1)。对于RAC波途径，还没有发现这种直接相互作用。在这里，我们报道了Rac和接头蛋白Nck通过WAVE1激活肌动蛋白成核的机制。WAVE1存在于一个异四聚体复合体中，它包括人PIR121(P53诱导的信使RNA，相对分子质量(M-r)为140,000)、Nap125(NCK相关蛋白，M-r为125,000)和HSPC300的同源物。而重组WAVE1是结构性活性的，而WAVE1复合体是无效的。因此，我们认为rac1和Nck引起WAVE1复合体的解离，从而释放活性的WAVE1-HSPC300并导致肌动蛋白成核。
Rac signalling to actin-a pathway that is thought to be mediated by the protein Scar/WAVE (WASP (Wiskott-Aldrich syndrome protein)-family verprolin homologous protein)-has a principal role in cell motility. In an analogous pathway, direct interaction of Cdc42 with the related protein N-WASP stimulates actin polymerization(1). For the Rac-WAVE pathway, no such direct interaction has been identified. Here we report a mechanism by which Rac and the adapter protein Nck activate actin nucleation through WAVE1. WAVE1 exists in a heterotetrameric complex that includes orthologues of human PIR121 (p53-inducible messenger RNA with a relative molecular mass (M-r)of 140,000), Nap125 (NCK-associated protein with an M-r of 125,000) and HSPC300. Whereas recombinant WAVE1 is constitutively active, the WAVE1 complex is inactive. We therefore propose that Rac1 and Nck cause dissociation of the WAVE1 complex, which releases active WAVE1-HSPC300 and leads to actin nucleation.