Spatial regulation of Raf kinase signaling by RKTG

被引：99

作者：

Feng, Lin ^{[1
]}

Xie, Xiaoduo ^{[1
]}

Ding, Qiurong ^{[1
]}

Luo, Xiaolin ^{[1
]}

He, Jing ^{[1
]}

Fan, Fengjuan ^{[1
]}

Liu, Weizhong ^{[1
]}

Wang, Zhenzhen ^{[1
]}

Chen, Yan ^{[1
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Grad Sch, Shanghai 200031, Peoples R China

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2007年 / 104卷 / 36期

关键词：

EGF; ERK; Golgi; Raf-1; Ras; PAQR3;

D O I：

10.1073/pnas.0701298104

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Subcellular compartmentalization has become an important theme in cell signaling such as spatial regulation of Ras by RasGRP1 and MEK/ERK by Sef. Here, we report spatial regulation of Raf kinase by RKTG (Raf kinase trapping to Golgi). RKTG is a seven-transmembrane protein localized at the Golgi apparatus. RKTG expression inhibits EGF-stimulated ERK and RSK phosphorylation, blocks NGF-mediated PC12 cell differentiation, and antagonizes Ras- and Raf-1 -stimulated Elk-1 transactivation. Through interaction with Raf-1, RKTG changes the localization of Raf-1 from cytoplasm to the Golgi apparatus, blocks EGF-stimulated Raf-1 membrane translocation, and reduces the interaction of Raf-1 with Ras and MEK1. In RKTG-null mice, the basal ERK phosphorylation level is increased in the brain and liver. In RKTG-deleted mouse embryonic fibroblasts, EGF-induced ERK phosphorylation is enhanced. Collectively, our results reveal a paradigm of spatial regulation of Raf kinase by RKTG via sequestrating Raf-1 to the Golgi apparatus and thereby inhibiting the ERK signaling pathway.

引用

页码：14348 / 14353

页数：6

共 40 条

[1] INDUCTION OF MEMBRANE RUFFLING AND FLUID-PHASE PINOCYTOSIS IN QUIESCENT FIBROBLASTS BY RAS PROTEINS [J].