Tehrani Shandiz, Tomasevic Nenad, Weed Scott, Sakowicz Roman, Cooper John A
Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):11933-8. doi: 10.1073/pnas.0701077104. Epub 2007 Jul 2.
Src kinase mediates growth factor signaling and causes oncogenic transformation, which includes dramatic changes in the actin cytoskeleton, cell shape, and motility. Cortactin was discovered as a substrate for Src. How phosphorylation of cortactin can enhance actin assembly is unknown. Here, using an actin assembly system reconstituted from purified components, we demonstrate for the first time a biochemical mechanism by which Src phosphorylation of cortactin affects actin assembly. The adaptor Nck is an important component of the system, linking phosphorylated cortactin with neuronal WASp (N-WASp) and WASp-interacting protein (WIP) to activate Arp2/3 complex.
Src激酶介导生长因子信号传导并导致致癌转化，这包括肌动蛋白细胞骨架、细胞形状和运动性的显著变化。皮层肌动蛋白被发现是Src的底物。皮层肌动蛋白的磷酸化如何增强肌动蛋白组装尚不清楚。在这里，我们使用由纯化成分重构的肌动蛋白组装系统，首次证明了皮层肌动蛋白的Src磷酸化影响肌动蛋白组装的生化机制。衔接蛋白Nck是该系统的重要组成部分，它将磷酸化的皮层肌动蛋白与神经WASp（N-WASp）和WASp相互作用蛋白（WIP）连接起来，以激活Arp2/3复合体。
