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首页> 外文期刊>Molecular and Cellular Biology >Activation of Rac1, RhoA, and mitogen-activated protein kinases is required for Ras transformation.
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Activation of Rac1, RhoA, and mitogen-activated protein kinases is required for Ras transformation.

机译：Ras转化需要激活Rac1，RhoA和有丝分裂原激活的蛋白激酶。

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Although substantial evidence supports a critical role for the activation of Raf-1 and mitogen-activated protein kinases (MAPKs) in oncogenic Ras-mediated transformation, recent evidence suggests that Ras may activate a second signaling pathway which involves the Ras-related proteins Rac1 and RhoA. Consequently, we used three complementary approaches to determine the contribution of Rac1 and RhoA function to oncogenic Ras-mediated transformation. First, whereas constitutively activated mutants of Rac1 and RhoA showed very weak transforming activity when transfected alone, their coexpression with a weakly transforming Raf-1 mutant caused a greater than 35-fold enhancement of transforming activity. Second, we observed that coexpression of dominant negative mutants of Rac1 and RhoA reduced oncogenic Ras transforming activity. Third, activated Rac1 and RhoA further enhanced oncogenic Ras-triggered morphologic transformation, as well as growth in soft agar and cell motility. Finally, we also observed that kinase-deficient MAPKs inhibited Ras transformation. Taken together, these data support the possibility that oncogenic Ras activation of Rac1 and RhoA, coupled with activation of the Raf/MAPK pathway, is required to trigger the full morphogenic and mitogenic consequences of oncogenic Ras transformation.
机译：尽管大量证据支持Raf-1和丝裂原激活的蛋白激酶（MAPK）的激活在致癌Ras介导的转化中发挥关键作用，但最近的证据表明Ras可能激活涉及Ras相关蛋白Rac1和Rac1的第二条信号通路。 RhoA。因此，我们使用三种互补的方法来确定Rac1和RhoA功能对致癌性Ras介导的转化的贡献。首先，虽然单独转染时，Rac1和RhoA的组成型激活突变体表现出非常弱的转化活性，但它们与弱转化Raf-1突变体的共表达导致转化活性提高了35倍以上。第二，我们观察到Rac1和RhoA的显性负突变体的共表达降低了致癌Ras转化活性。第三，活化的Rac1和RhoA进一步增强了致癌的Ras触发的形态转化，以及软琼脂的生长和细胞运动性。最后，我们还观察到激酶缺失的MAPK抑制了Ras转化。综上所述，这些数据支持可能需要触发Rac1和RhoA的致癌性Ras激活以及Raf / MAPK途径的激活，才能触发致癌性Ras转化的完全形态和有丝分裂作用。

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