PAQR10 and PAQR11 mediate Ras signaling in the Golgi apparatus  

作　　者：Ting Jin Qiurong Ding Heng Huang Daqian Xu Yuhui Jiang Ben Zhou Zhenghu Li Xiaomeng Jiang Jing He Weizhong Liu Yixuan Zhang Yi Pan Zhenzhen Wang Walter G Thomas Yan Chen 

机构地区：[1]Key Laboratory of Nutrition and Metabolism,Institute for Nutritional Sciences,Shanghai Institutes for Biological Sciences,Graduate School of the Chinese Academy of Sciences,Chinese Academy of Sciences,Shanghai 200031,China [2]School of Biomedical Sciences,University of Queensland,Brisbane,Australia

出　　处：《Cell Research》2012年第4期661-676,共16页细胞研究（英文版）

基　　金：Acknowledgments We thank Drs Natlie G Ahn （University of Colorado）, Piero Crespo （Consejo Superior de Investigaciones CientFficas）, Xos6 R Bustelo （University of Salamanca）, Robert J Kay （University of British Columbia） and Juan S Bonifacino （National Institute of Child Health and Human Development） for generously providing the plasmids. This work was supported by research grants from Ministry of Science and Technology of China （2007CB947100 to YC and 2010CB529506 to YP and ZW）, National Natural Science Foundation of China （30830037 and 81021002 to YC and 30971660 to YP）, Chinese Academy of Sciences （KSCX2- EW-R-08 to YC.）, and Shanghai Institutes for Biological Sciences （2009KIP207 to YP）.

摘　　要：Ras plays a pivotal role in many cellular activities, and its subcellular compartmentalization provides spatial and temporal selectivity. Here we report a mode of spatial regulation of Ras signaling in the Golgi apparatus by two highly homologous proteins PAQR10 and PAQRll of the progestin and AdipoQ receptors family. PAQRI0 and PAQRll are exclusively localized in the Golgi apparatus. Overexpression of PAQR10/PAQRll stimulates basal and EGF-induced ERK phosphorylation and increases the expression of ERK target genes in a dose-dependent man- ner. Overexpression of PAQR10/PAQRll markedly elevates Golgi localization of HRas, NRas and KRas4A, but not KRas4B. PAQR10 and PAQRll can also interact with HRas, NRas and KRas4A, but not KRas4B. The increased Ras protein at the Golgi apparatus by overexpression of PAQR10/PAQRll is in an active state. Consistently, knockdown of PAQR10 and PAQRll reduces EGF-stimulated ERK phosphorylation and Ras activation at the Golgi apparatus. Intriguingly, PAQR10 and PAQRll are able to interact with RasGRP1, a guanine nucleotide exchange protein of Ras, and increase Golgi localization of RasGRP1. The C1 domain of RasGRP1 is both necessary and sufficient for the interaction of RasGRP1 with PAQR10/PAQRll. The simulation of ERK phosphorylation by overexpressed PAQR10/ PAQRll is abrogated by downregulation of RasGRP1. Furthermore, differentiation of PC12 cells is significantly enhanced by overexpression of PAQR10/PAQRll. Collectively, this study uncovers a new paradigm of spatial regulation of Ras signaling in the Golgi apparatus by PAQR10 and PAQRll.

关 键 词：RAS Signal transduction Golgi apparatus COMPARTMENTALIZATION ERK 

分 类 号：Q516[生物学—生物化学] TP393[自动化与计算机技术—计算机应用技术]