AN ESSENTIAL ROLE FOR RAC IN RAS TRANSFORMATION
AN ESSENTIAL ROLE FOR RAC IN RAS TRANSFORMATION
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DOI：
10.1038/374457a0
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发表时间：
1995-03-30
期刊：
影响因子：
64.8
通讯作者：
SYMONS, M
中科院分区：
文献类型：
--
作者：
QIU, RG;CHEN, J;SYMONS, M
GTPase Rac(1) 是生长因子或致癌 Ras(1) 诱导的肌动蛋白细胞骨架重组的关键成分。在这里，我们研究了 Rac(1) 在细胞转化中的作用，并表明表达激活的 Val-12 Rac(1)（Rac(1) 在残基 12 处带有缬氨酸）的 Rat(1) 成纤维细胞显示出恶性转化的所有特征。在 NIH3T3 成纤维细胞的焦点形成测定中，为了测量转化效率，我们发现显性失活的 Asn-17 Rac(1) 抑制致癌 Ras 的焦点形成，但不抑制 RafCAAX 的焦点形成，RafCAAX 是一种通过添加来自 K-Ras 的羧基末端定位信号而靶向质膜的 Raf 激酶。这表明Rac对于Ras的转化是必需的。此外，Val-12 Rac(1) 在病灶形成测定中与 RafCAAX 强烈协同作用，表明致癌 Ras 驱动 Rac 和 MAP 激酶途径，这两种途径共同导致转化。
THE GTPase Rac(1) is a key component in the reorganization of the actin cytoskeleton that is induced by growth factors or oncogenic Ras(1). Here we investigate the role of Rac(1) in cell transformation and show that Rat(1) fibroblasts expressing activated Val-12 Rac(1) (Rac(1) with valine at residue 12) display all the hallmarks of malignant transformation. In a focus-forming assay in NIH3T3 fibroblasts to measure the efficiency of transformation, we found that dominant-negative Asn-17 Rac(1) inhibited focus formation by oncogenic Ras, but not by RafCAAX, a Raf kinase targeted to the plasma membrane by virtue of the addition of a carboxyterminal localization signal from K-Ras. This indicates that Rac is essential for transformation by Ras. In addition, Val-12 Rac(1) synergizes strongly with RafCAAX in focus-formation assays, indicating that oncogenic Ras drives both the Rac and MAP-kinase pathways, which cooperate to cause transformation.