Bottorff D, Stang S, Agellon S, Stone J C
Department of Biochemistry, University of Alberta, Edmonton, Canada.
Mol Cell Biol. 1995 Sep;15(9):5113-22. doi: 10.1128/MCB.15.9.5113.
A mutant rat cell clone that suppresses the transformation defects of RAS effector loop substitutions is heterozygous for mutations in c-raf1 and MEK1. The mutant cells can be transformed by many otherwise defective RAS effector mutants, including RAS genes with the effector regions of distantly related GTPases, even though the encoded RAS proteins do not interact with either the mutant or wild-type RAF in Saccharomyces cerevisiae. While the significance of the c-raf1 mutation is unclear, the MEK1 mutation increases MEK1 activity and leads to activation of mitogen-activated protein kinase. The mutant MEK1 is coupled to the epidermal growth factor pathway but exhibits decreased physical interaction with RAF. When overexpressed, the MEK1 mutation is transforming and causes hyperphosphorylation of RAF. Signalling from RAS to MEK1 may be mediated by something other than RAF alone, but signalling through MEK1 is probably sufficient for RAS transformation.
一个能抑制RAS效应环替代物转化缺陷的突变大鼠细胞克隆，在c-raf1和MEK1基因中存在杂合突变。这些突变细胞可被许多原本有缺陷的RAS效应突变体转化，包括带有远缘相关GTP酶效应区域的RAS基因，尽管编码的RAS蛋白在酿酒酵母中不与突变型或野生型RAF相互作用。虽然c-raf1突变的意义尚不清楚，但MEK1突变会增加MEK1活性并导致丝裂原活化蛋白激酶的激活。突变的MEK1与表皮生长因子途径偶联，但与RAF的物理相互作用减少。当过度表达时，MEK1突变具有转化作用并导致RAF的过度磷酸化。从RAS到MEK1的信号传导可能不仅仅由RAF单独介导，但通过MEK1的信号传导可能足以实现RAS转化。
