Stimulation of membrane ruffling and MAP kinase activation by distinct effectors of RAS
Stimulation of membrane ruffling and MAP kinase activation by distinct effectors of RAS
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DOI：
10.1126/science.271.5250.810
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发表时间：
1996-02-09
期刊：
影响因子：
56.9
通讯作者：
BarSagi, D
中科院分区：
文献类型：
--
作者：
Joneson, T;White, MA;BarSagi, D
RAS鸟嘌呤核苷酸结合蛋白激活调节细胞生长和分化的多种信号传导事件。在静止的成纤维细胞中，活化的H-RAS（H-RAS（V12），其中V12表示缬氨酸-12）的异位表达诱导膜皱褶、促分裂原活化蛋白（MAP）激酶活化和DNA合成的刺激。鉴定了活化的H-RAS的突变体H-RAS（V12C40）（其中C40表示半胱氨酸-40），其对于MAP激酶活化和DNA合成的刺激是缺陷的，但保留了诱导膜皱褶的能力。活化的H-RAS的另一种突变体H-RAS（V12S35）（其中S35表示丝氨酸-35），其活化MAP激酶，在刺激膜皱褶和诱导DNA合成方面有缺陷。两种突变体的表达导致DNA合成的刺激，其与H-RAS（V12）诱导的DNA合成相当。这些结果表明，膜皱褶和激活MAP激酶代表不同的RAS效应途径，从这两个途径的输入是必需的RAS的促有丝分裂活性。
The RAS guanine nucleotide binding proteins activate multiple signaling events that regulate cell growth and differentiation. In quiescent fibroblasts, ectopic expression of activated H-RAS (H-RAS(V12), where V12 indicates valine-12) induces membrane ruffling, mitogen-activated protein (MAP) kinase activation, and stimulation of DNA synthesis. A mutant of activated H-RAS, H-RAS(V12C40) (where C40 indicates cysteine-40), was identified that was defective for MAP kinase activation and stimulation of DNA synthesis, but retained the ability to induce membrane ruffling. Another mutant of activated H-RAS, H-RAS(V12S35) (where S35 indicates serine-35), which activates MAP kinase, was defective for stimulation of membrane ruffling and induction of DNA synthesis. Expression of both mutants resulted in a stimulation of DNA synthesis that was comparable to that induced by H-RAS(V12). These results indicate that membrane ruffling and activation of MAP kinase represent distinct RAS effector pathways and that input from both pathways is required for the mitogenic activity of RAS.