Rodriguez-Viciana P, Warne P H, Khwaja A, Marte B M, Pappin D, Das P, Waterfield M D, Ridley A, Downward J
Imperial Cancer Research Fund, London, United Kingdom.
Cell. 1997 May 2;89(3):457-67. doi: 10.1016/s0092-8674(00)80226-3.
The pathways by which mammalian Ras proteins induce cortical actin rearrangement and cause cellular transformation are investigated using partial loss of function mutants of Ras and activated and inhibitory forms of various postulated target enzymes for Ras. Efficient transformation by Ras requires activation of other direct effectors in addition to the MAP kinase kinase kinase Raf and is inhibited by inactivation of the PI 3-kinase pathway. Actin rearrangement correlates with the ability of Ras mutants to activate PI 3-kinase. Inhibition of PI 3-kinase activity blocks Ras induction of membrane ruffling, while activated PI 3-kinase is sufficient to induce membrane ruffling, acting through Rac. The ability of activated Ras to stimulate PI 3-kinase in addition to Raf is therefore important in Ras transformation of mammalian cells and essential in Ras-induced cytoskeletal reorganization.
利用Ras的功能部分缺失突变体以及各种假定的Ras靶酶的激活形式和抑制形式，研究了哺乳动物Ras蛋白诱导皮质肌动蛋白重排并导致细胞转化的途径。Ras的有效转化除了需要丝裂原活化蛋白激酶激酶激酶Raf之外，还需要激活其他直接效应器，并且受到PI 3-激酶途径失活的抑制。肌动蛋白重排与Ras突变体激活PI 3-激酶的能力相关。抑制PI 3-激酶活性可阻断Ras诱导的膜 ruffling，而激活的PI 3-激酶足以通过Rac诱导膜ruffling。因此，激活的Ras除了刺激Raf之外还能刺激PI 3-激酶的能力在哺乳动物细胞的Ras转化中很重要，并且在Ras诱导的细胞骨架重组中必不可少。
