Rocks Oliver, Peyker Anna, Kahms Martin, Verveer Peter J, Koerner Carolin, Lumbierres Maria, Kuhlmann Jürgen, Waldmann Herbert, Wittinghofer Alfred, Bastiaens Philippe I H
Department of Structural Biology, Max Planck Institute for Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany.
Science. 2005 Mar 18;307(5716):1746-52. doi: 10.1126/science.1105654. Epub 2005 Feb 10.
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.
我们发现，H-和Nras鸟苷三磷酸结合蛋白的特定亚细胞分布是由一个组成性的去/再酰化循环产生的，该循环作用于棕榈酰化蛋白，驱动它们在质膜（PM）和高尔基体之间快速交换。去棕榈酰化使法尼基化的Ras在所有膜中重新分布，随后再棕榈酰化并将Ras捕获在高尔基体，从那里它通过分泌途径被重新导向质膜。这个连续的循环防止Ras在内膜上非特异性停留，从而维持特定的细胞内区室化。去/再酰化循环还通过质膜定位的Ras鸟苷三磷酸的转运在高尔基体处启动Ras激活。不同的去/再棕榈酰化动力学解释了对生长因子的异构体特异性激活反应。
