Ras, an actor on many stages: posttranslational modifications, localization, and site-specified events.
Ras, an actor on many stages: posttranslational modifications, localization, and site-specified events.
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DOI：
10.1177/1947601911409213
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发表时间：
2011-03-01
期刊：
影响因子：
--
通讯作者：
Crespo, Piero
中科院分区：
文献类型：
--
作者：
Arozarena, Imanol;Calvo, Fernando;Crespo, Piero
在我们过去十年收集的关于拉斯的大量信息中，空间概念在该领域的引入构成了一场重大革命，使拉斯之谜的许多部分得以解决。在早期，人们认为Ras只在质膜上发挥作用。今天，我们知道在质膜内，3种Ras亚型-H-Ras、K-Ras和N-Ras-占据不同的微区，并且这些亚型也存在于内膜中并具有活性。我们还发现Ras蛋白与这些定位并不是静态相关的;相反，它们在区室之间动态流动。我们已经了解到，在这些定位中，Ras处于位点特异性调节机制下，独特地参与效应子途径并开启不同的遗传程序以产生不同的生物反应。所有这些过程在很大程度上都是可能的，这是由于Ras蛋白与膜结合的翻译后修饰以及Ras所经历的磷酸化和泛素化等调节事件。因此，空间和这些控制机制共同作用，赋予Ras信号巨大的信号可变性，使其可能具有多种生物学作用。这些数据已经建立了这样的概念，即Ras信号不是一个单一的同质实体，而是由多个特定于位点的子信号的整合产生的，Ras已经成为空间如何差异地塑造信号的范例。
Among the wealth of information that we have gathered about Ras in the past decade, the introduction of the concept of space in the field has constituted a major revolution that has enabled many pieces of the Ras puzzle to fall into place. In the early days, it was believed that Ras functioned exclusively at the plasma membrane. Today, we know that within the plasma membrane, the 3 Ras isoforms-H-Ras, K-Ras, and N-Ras-occupy different microdomains and that these isoforms are also present and active in endomembranes. We have also discovered that Ras proteins are not statically associated with these localizations; instead, they traffic dynamically between compartments. And we have learned that at these localizations, Ras is under site-specific regulatory mechanisms, distinctively engaging effector pathways and switching on diverse genetic programs to generate different biological responses. All of these processes are possible in great part due to the posttranslational modifications whereby Ras proteins bind to membranes and to regulatory events such as phosphorylation and ubiquitination that Ras is subject to. As such, space and these control mechanisms act in conjunction to endow Ras signals with an enormous signal variability that makes possible its multiple biological roles. These data have established the concept that the Ras signal, instead of being one single, homogeneous entity, results from the integration of multiple, site-specified subsignals, and Ras has become a paradigm of how space can differentially shape signaling.