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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Ding, Qiurong Luo, Xiaolin Fan, Fengjuan Wang, Zhenzhen Xie, Xiaoduo Feng, Lin He, Jing Liu, Weizhong Chen, Yan |
| Description | Author Affiliation: Feng L ( Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China.); |
| Abstract | 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 36 |
| Volume Number | 104 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2007-09-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Intracellular Signaling Peptides And Proteins Metabolism MAP Kinase Signaling System Raf Kinases Amino Acid Sequence Animals Cell Membrane Cells, Cultured Gene Deletion Golgi Apparatus Chemistry Deficiency Genetics Mice Mice, Knockout Molecular Sequence Data Protein Binding Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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