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首页> 外文期刊>Molecular and Cellular Biology >Distinct Utilization of Effectors and Biological Outcomes Resulting from Site-Specific Ras Activation: Ras Functions in Lipid Rafts and Golgi Complex Are Dispensable for Proliferation and Transformation
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Distinct Utilization of Effectors and Biological Outcomes Resulting from Site-Specific Ras Activation: Ras Functions in Lipid Rafts and Golgi Complex Are Dispensable for Proliferation and Transformation

机译：特异利用Ras激活引起的效应子和生物学结果：脂质筏和高尔基体中的Ras功能对于增殖和转化是必不可少的

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Ras proteins are distributed in different types of plasma membrane microdomains and endomembranes. However, how microlocalization affects the signals generated by Ras and its subsequent biological outputs is largely unknown. We have approached this question by selectively targeting RasV12 to different cellular sublocalizations. We show here that compartmentalization dictates Ras utilization of effectors and the intensity of its signals. Activated Ras can evoke enhanced proliferation and transformation from most of its platforms, with the exception of the Golgi complex. Furthermore, signals that promote survival emanate primarily from the endoplasmic reticulum pool. In addition, we have investigated the need for the different pools of endogenous Ras in the conveyance of upstream mitogenic and transforming signals. Using targeted RasN17 inhibitory mutants and in physiological contexts such as H-Ras/N-Ras double knockout fibroblasts, we demonstrate that Ras functions at lipid rafts and at the Golgi complex are fully dispensable for proliferation and transformation.
机译：Ras蛋白分布在不同类型的质膜微区和内膜中。但是，微定位如何影响Ras产生的信号及其随后的生物学输出在很大程度上尚不清楚。我们通过选择性地将RasV12靶向不同的细胞亚定位来解决这个问题。我们在这里表明，区室化决定了效应子的Ras利用率及其信号强度。活化的Ras可以引起其大多数平台上增强的增殖和转化，但高尔基复合体除外。此外，促进生存的信号主要来自内质网池。另外，我们已经研究了上游有丝分裂和转化信号的传递中内源性Ras的不同库的需求。使用有针对性的RasN17抑制突变体，并在诸如H-Ras / N-Ras双敲除成纤维细胞的生理环境中，我们证明了Ras在脂质筏和高尔基体上的功能对于增殖和转化是完全必要的。

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