Comparative proteomic analysis of compartmentalised Ras signalling.
Comparative proteomic analysis of compartmentalised Ras signalling.
复制标题
DOI：
10.1038/srep17307
复制
发表时间：
2015-12-01
影响因子：
4.6
通讯作者：
Prior IA
中科院分区：
文献类型：
--
作者：
Hernandez-Valladares M;Prior IA
Ras蛋白是从细胞表面和内膜隔室两者操作的膜结合信号枢纽。然而，在何种程度上细胞内池的Ras可以有助于细胞信号传导是有争议的。为了解决这个问题，我们已经进行了分区Ras信号的全球屏幕。我们发现，虽然ER/高尔基体-和内体-Ras仅产生弱输出，但定位于线粒体或高尔基体的Ras显著且明显地影响所分析的多种蛋白质的丰度和磷酸化。我们的数据显示，与对照相比，约80%的磷酸化位点表现出较大的变化（≥1.5倍），可以通过细胞器Ras信号转导进行调节。预计大多数区室化Ras特异性反应会影响基因表达、RNA剪接和细胞增殖。我们的分析加强了这一概念，即区室化影响Ras信号传导，并提供了详细的了解内膜Ras信号传导下游反应的广泛调制。
Ras proteins are membrane bound signalling hubs that operate from both the cell surface and endomembrane compartments. However, the extent to which intracellular pools of Ras can contribute to cell signalling is debated. To address this, we have performed a global screen of compartmentalised Ras signalling. We find that whilst ER/Golgi- and endosomal-Ras only generate weak outputs, Ras localised to the mitochondria or Golgi significantly and distinctly influence both the abundance and phosphorylation of a wide range of proteins analysed. Our data reveal that ~80% of phosphosites exhibiting large (≥1.5-fold) changes compared to control can be modulated by organellar Ras signalling. The majority of compartmentalised Ras-specific responses are predicted to influence gene expression, RNA splicing and cell proliferation. Our analysis reinforces the concept that compartmentalisation influences Ras signalling and provides detailed insight into the widespread modulation of responses downstream of endomembranous Ras signalling.