Rohatgi R, Ma L, Miki H, Lopez M, Kirchhausen T, Takenawa T, Kirschner M W
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Cell. 1999 Apr 16;97(2):221-31. doi: 10.1016/s0092-8674(00)80732-1.
Although small GTP-binding proteins of the Rho family have been implicated in signaling to the actin cytoskeleton, the exact nature of the linkage has remained obscure. We describe a novel mechanism that links one Rho family member, Cdc42, to actin polymerization. N-WASP, a ubiquitously expressed Cdc42-interacting protein, is required for Cdc42-stimulated actin polymerization in Xenopus egg extracts. The C terminus of N-WASP binds to the Arp2/3 complex and dramatically stimulates its ability to nucleate actin polymerization. Although full-length N-WASP is less effective, its activity can be greatly enhanced by Cdc42 and phosphatidylinositol (4,5) bisphosphate. Therefore, N-WASP and the Arp2/3 complex comprise a core mechanism that directly connects signal transduction pathways to the stimulation of actin polymerization.
尽管Rho家族的小GTP结合蛋白与肌动蛋白细胞骨架的信号传导有关，但其联系的确切性质仍不清楚。我们描述了一种将Rho家族成员之一Cdc42与肌动蛋白聚合联系起来的新机制。N-WASP是一种普遍表达的与Cdc42相互作用的蛋白，爪蟾卵提取物中Cdc42刺激的肌动蛋白聚合需要它。N-WASP的C末端与Arp2/3复合体结合，并显著刺激其引发肌动蛋白聚合的能力。尽管全长N-WASP的效果较差，但其活性可被Cdc42和磷脂酰肌醇（4,5）二磷酸大大增强。因此，N-WASP和Arp2/3复合体构成了一个直接将信号转导途径与肌动蛋白聚合刺激联系起来的核心机制。
