PAQR10 and PAQR11 mediate Ras signaling in the Golgi apparatus

Jin, Ting, Ding, Quirong, Huang, Heng, Xu, Daqian, Jiang, Yuhui, Zhou, Ben, Li, Zhenghu, Jiang, Xiaomeng, He, Jing, Liu, Weizhong, Zhang, Yixuan, Pan, Yi, Wang, Zhezhen, Thomas, Walter G. and Chen, Yan (2012) PAQR10 and PAQR11 mediate Ras signaling in the Golgi apparatus. Cell Research, 22 4: 661-676. doi:10.1038/cr.2011.161

Author Jin, Ting
Ding, Quirong
Huang, Heng
Xu, Daqian
Jiang, Yuhui
Zhou, Ben
Li, Zhenghu
Jiang, Xiaomeng
He, Jing
Liu, Weizhong
Zhang, Yixuan
Pan, Yi
Wang, Zhezhen
Thomas, Walter G.
Chen, Yan
Title PAQR10 and PAQR11 mediate Ras signaling in the Golgi apparatus
Journal name Cell Research   Check publisher's open access policy
ISSN 1001-0602
Publication date 2012-04
Year available 2011
Sub-type Article (original research)
DOI 10.1038/cr.2011.161
Volume 22
Issue 4
Start page 661
End page 676
Total pages 16
Place of publication London, England, U.K.
Publisher Nature Publishing Group
Collection year 2012
Language eng
Abstract 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 PAQR11 of the progestin and AdipoQ receptors family. PAQR10 and PAQR11 are exclusively localized in the Golgi apparatus. Overexpression of PAQR10/PAQR11 stimulates basal and EGF-induced ERK phosphorylation and increases the expression of ERK target genes in a dose-dependent manner. Overexpression of PAQR10/PAQR11 markedly elevates Golgi localization of HRas, NRas and KRas4A, but not KRas4B. PAQR10 and PAQR11 can also interact with HRas, NRas and KRas4A, but not KRas4B. The increased Ras protein at the Golgi apparatus by overexpression of PAQR10/PAQR11 is in an active state. Consistently, knockdown of PAQR10 and PAQR11 reduces EGF-stimulated ERK phosphorylation and Ras activation at the Golgi apparatus. Intriguingly, PAQR10 and PAQR11 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/PAQR11. The simulation of ERK phosphorylation by overexpressed PAQR10/PAQR11 is abrogated by downregulation of RasGRP1. Furthermore, differentiation of PC12 cells is significantly enhanced by overexpression of PAQR10/PAQR11. Collectively, this study uncovers a new paradigm of spatial regulation of Ras signaling in the Golgi apparatus by PAQR10 and PAQR11.
Keyword Ras
Signal transduction
Golgi apparatus
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Advance online publication 4 October 2011

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Biomedical Sciences Publications
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Created: Tue, 21 Feb 2012, 14:00:25 EST by Bacsweet Kaur on behalf of School of Biomedical Sciences