Ras-independent transformation by v-Src.
Ras-independent transformation by v-Src.
复制标题
v-Src 的 Ras 独立转化。
DOI：
10.1073/pnas.94.7.3028
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发表时间：
1997
影响因子：
11.1
通讯作者：
Martin,GS
中科院分区：
文献类型：
--
作者：
Aftab,DT;Kwan,J;Martin,GS
多种受体和非受体酪氨酸激酶的信号转导是由膜相关的GTP酶RAS介导的。转化型非受体酪氨酸激酶v-Src的表达导致Ras的激活，抑制NIH3T3细胞的RAS功能抑制了v-Src的转化，表明在这些细胞中，v-Src发挥其生物学效应需要依赖于RAS的信号通路。然而，我们在这里发现，在野生型v-Src转化的大鼠2成纤维细胞和SRX5转化的鸡胚胎成纤维细胞中，RAS不被激活。SRX5是一个v-Src突变体，在自动磷酸化的主要位置插入了一个连接子。显性负性RAS突变体的表达完全抑制了v-Src激活RAS下游的丝裂原活化蛋白激酶ERK2的能力。然而，从不同的标准来看，显性负值RAS并不抑制v-Src的转化。因此，在没有RAS激活或RAS刺激的ERK2活性的情况下，v-Src至少可以转化某些类型的细胞，因此在这些细胞中，RAS非依赖的信号通路的激活必须足以进行转化。
Signaling by a variety of receptor and nonreceptor tyrosine kinases is mediated by Ras, a membrane-associated GTPase. Expression of v-Src, a transforming nonreceptor tyrosine kinase, results in Ras activation, and inhibition of Ras function in NIH 3T3 cells suppresses transformation by v-Src, indicating that in these cells Ras-dependent signaling pathways are required for v-Src to exert its biological effects. However, we show here that Ras was not activated in Rat-2 fibroblasts transformed by wild-type v-Src, or in chicken embryo fibroblasts transformed by SRX5, a v-Src mutant with a linker insertion at the major site of autophosphorylation. Expression of a dominant-negative mutant of Ras completely inhibited the ability of v-Src to activate the mitogen-activated protein kinase ERK2, which is downstream of Ras. However, dominant-negative Ras did not suppress transformation by v-Src as judged by a variety of criteria. Thus, v-Src can transform at least some cell types in the absence of Ras activation or Ras-stimulated ERK2 activity, and in these cells activation of Ras-independent signaling pathways must therefore be sufficient for transformation.