Eden Sharon, Rohatgi Rajat, Podtelejnikov Alexandre V, Mann Matthias, Kirschner Marc W
Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue Boston, Massachusetts 02115, USA.
Nature. 2002 Aug 15;418(6899):790-3. doi: 10.1038/nature00859.
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. 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.
Rac向肌动蛋白发出信号——这一信号通路被认为是由Scar/WAVE蛋白（Wiskott-Aldrich综合征蛋白（WASP）家族维普洛林同源蛋白）介导的——在细胞运动中起主要作用。在类似的信号通路中，Cdc42与相关蛋白N-WASP的直接相互作用会刺激肌动蛋白聚合。对于Rac-WAVE信号通路，尚未发现这种直接相互作用。在此，我们报告一种机制，通过该机制Rac和衔接蛋白Nck可通过WAVE1激活肌动蛋白成核。WAVE1存在于一种异源四聚体复合物中，该复合物包含人类PIR121（相对分子质量（M(r)）为140,000的p53诱导信使RNA）、Nap125（M(r)为125,000的NCK相关蛋白）和HSPC300的直系同源物。虽然重组WAVE1具有组成型活性，但WAVE1复合物无活性。因此，我们提出Rac1和Nck会导致WAVE1复合物解离，从而释放出有活性的WAVE1-HSPC300并引发肌动蛋白成核。
