White M A, Vale T, Camonis J H, Schaefer E, Wigler M H
Department of Cell Biology and Neuroscience, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9039, USA.
J Biol Chem. 1996 Jul 12;271(28):16439-42. doi: 10.1074/jbc.271.28.16439.
Oncogenic Ras transforms cells through the activation of multiple downstream pathways mediated by separate effector molecules, one of which is Raf. Here we report the identification of a second ras-binding protein that can induce cellular transformation in parallel with activation of the Raf/mitogen-activated protein kinase cascade. The Ral guanine nucleotide dissociation stimulator (RalGDS) was isolated from a screen for Ras-binding proteins that specifically interact with a Ras effector-loop mutant, ras(12V,37G), that uncouples Ras from activation of Raf1. RalGDS, like ras(12V, 37G), cooperates synergistically with mutationally activated Raf to induce foci of growth and morphologically transformed NIH 3T3 cells. RalGDS does not significantly enhance MAP kinase activation by activated Raf, suggesting that the cooperativity in focus formation is due to a distinct pathway acting downstream of Ras and parallel to Raf.
致癌性Ras通过由不同效应分子介导的多个下游途径的激活来转化细胞，其中之一是Raf。在此我们报告鉴定出一种第二个Ras结合蛋白，其可与Raf/丝裂原活化蛋白激酶级联的激活并行诱导细胞转化。Ral鸟嘌呤核苷酸解离刺激因子（RalGDS）是从对Ras结合蛋白的筛选中分离出来的，这些蛋白与Ras效应环突变体ras(12V,37G)特异性相互作用，该突变体使Ras与Raf1的激活解偶联。RalGDS与ras(12V, 37G)一样，与突变激活的Raf协同作用，诱导生长灶和形态转化的NIH 3T3细胞。RalGDS不会显著增强激活的Raf对MAP激酶的激活，这表明灶形成中的协同作用是由于Ras下游且与Raf平行的一条不同途径。
