An acylation cycle regulates localization and activity of palmitoylated Ras isoforms
An acylation cycle regulates localization and activity of palmitoylated Ras isoforms
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DOI：
10.1126/science.1105654
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发表时间：
2005-03-18
期刊：
影响因子：
56.9
通讯作者：
Bastiaens, PIH
中科院分区：
文献类型：
--
作者：
Rocks, O;Peyker, A;Bastiaens, PIH
我们发现H-和NRAS鸟苷三磷酸结合蛋白的特殊亚细胞分布是由一个结构性的去/反应循环产生的，该循环作用于棕榈酰化的蛋白质，驱动它们在质膜(PM)和高尔基体之间的快速交换。Depalmito化在所有膜上重新分布法尼化的RAS，然后在高尔基体处重新棕榈酰化和捕获RAS，从那里通过分泌途径重定向到PM。这个连续的循环阻止RAS非特异性地滞留在细胞内膜上，从而维持特定的细胞内区划。去酰化循环还通过运输PM定位的RAS鸟苷三磷酸在高尔基体启动RAS的激活。不同的脱棕榈酸化/复棕榈酸化动力学解释了异构体对生长因子的特异性激活反应。
We show that the specific subcellular distribution of H- and Nras guanosine triphosphate-binding proteins is generated by a constitutive de/reacylation cycle that operates on palmitoylated proteins, driving their rapid exchange between the plasma membrane (PM) and the Golgi apparatus. Depalmitoylation redistributes farnesylated Ras in all membranes, followed by repalmitoylation and trapping of Ras at the Golgi, from where it is redirected to the PM via the secretory pathway. This continuous cycle prevents Ras from nonspecific residence on endomembranes, thereby maintaining the specific intracellular compartmentalization. The de/reacylation cycle also initiates Ras activation at the Golgi by transport of PM-localized Ras guanosine triphosphate. Different de/repalmitoylation kinetics account for isoform-specific activation responses to growth factors.