Wang W, Fisher E M, Jia Q, Dunn J M, Porfiri E, Downward J, Egan S E
Division of Immunology and Cancer Research, Hospital for Sick Children, Toronto, Ontario, Canada.
Nat Genet. 1995 Jul;10(3):294-300. doi: 10.1038/ng0795-294.
Cellular Ras proteins are activated primarily by specific guanine-nucleotide releasing factors such as the Son of Sevenless (Sos) proteins. This activation event is thought to occur in response to plasma membrane localization of a complex containing Sos and a small adapter protein Grb2. We have isolated a dominant mutant allele of mSos1 which transforms Rat1 cells, yet is no longer able to bind Grb2. Biochemical experiments reveal that the subcellular distribution of this truncated Sos protein is not altered with respect to the wild type Sos protein. These data argue against a role for Grb2 in the direct recruitment of Sos proteins to the plasma membrane and suggest that Grb2 may function to overcome negative regulation of Sos by its C terminus.
细胞Ras蛋白主要由特定的鸟嘌呤核苷酸释放因子激活，如七号less之子（Sos）蛋白。这种激活事件被认为是对包含Sos和小衔接蛋白Grb2的复合物定位于质膜的反应。我们分离出了mSos1的一个显性突变等位基因，它能转化大鼠1细胞，但不再能够结合Grb2。生化实验表明，这种截短的Sos蛋白的亚细胞分布相对于野生型Sos蛋白没有改变。这些数据反对Grb2在将Sos蛋白直接招募到质膜中的作用，并表明Grb2可能起到克服Sos的C末端对其负调控的作用。
