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Role for engagement of-arrestin2 by the transactivated EGFR in agonist-specific regulation of receptor activation of ERK1/2

文献类型：期刊论文

作者Zhang, Le-Sha2,3; Wang, Yu-Jun2,3; Ju, Yun-Yue2,3; Zan, Gui-Ying2,3; Xu, Chi2,3; Hong, Min-Hua2,3; Wang, Yu-Hua1; Chi, Zhi-Qiang2,3; Liu, Jing-Gen2,3
刊名BRITISH JOURNAL OF PHARMACOLOGY
出版日期2015-10
卷号172期号:20页码:4847-4863
ISSN号0007-1188
DOI10.1111/bph.13254
文献子类Article
英文摘要Background and Purpose-Arrestins function as signal transducers linking GPCRs to ERK1/2 signalling either by scaffolding members of ERK1/2s cascades or by transactivating receptor tyrosine kinases through Src-mediated release of transactivating factor. Recruitment of -arrestins to the activated GPCRs is required for ERK1/2 activation. Our previous studies showed that receptors activate ERK1/2 through a -arrestin-dependent mechanism without inducing -arrestin binding to the receptors. However, the precise mechanisms involved remain to be established. Experimental ApproachERK1/2 activation by receptor ligands was assessed using HEK293 cells in vitro and male Sprague Dawley rats in vivo. Immunoprecipitation, immunoblotting, siRNA transfection, intracerebroventricular injection and immunohistochemistry were used to elucidate the underlying mechanism. Key ResultsWe identified a new signalling pathway in which recruitment of -arrestin2 to the EGFR rather than receptor was required for its role in receptor-mediated ERK1/2 activation in response to H-Tyr-Tic-Phe-Phe-OH (TIPP) or morphine stimulation. Stimulation of the receptor with ligands leads to the phosphorylation of PKC, which acts upstream of EGFR transactivation and is needed for the release of the EGFR-activating factor, whereas -arrestin2 was found to act downstream of the EGFR transactivation. Moreover, we demonstrated that coupling of the PKC/EGFR/-arrestin2 transactivation pathway to receptor-mediated ERK1/2 activation was ligand-specific and the Ser(363) of receptors was crucial for ligand-specific implementation of this ERK1/2 activation pathway. Conclusions and ImplicationsThe receptor-mediated activation of ERK1/2 is via ligand-specific transactivation of EGFR. This study adds new insights into the mechanism by which receptors activate ERK1/2.
WOS关键词DELTA-OPIOID RECEPTOR ; EPIDERMAL-GROWTH-FACTOR ; PROTEIN-COUPLED RECEPTORS ; BETA(2) ADRENERGIC-RECEPTOR ; FACTOR-I RECEPTOR ; KINASE-C-DELTA ; PHOSPHOLIPASE-C ; CONCISE GUIDE ; ARRIVE GUIDELINES ; ARRESTIN
资助项目Ministry of Science and Technology of China[2013CB835100] ; Ministry of Science and Technology of China[2009CB522005] ; Ministry of Science and Technology of China[2012ZX09301001-005] ; Ministry of Science and Technology of China[2012BAI01B00] ; National Natural Science Foundation of China[81130087] ; National Natural Science Foundation of China[91232716] ; Committee of Science and Technology of Shanghai[13JC140680] ; Committee of Science and Technology of Jiangsu Province[BK2012457] ; Priority Academic Program Development of Jiangsu Higher Education Institutions[00000000]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000363656000006
出版者WILEY
源URL[http://119.78.100.183/handle/2S10ELR8/276380]  
专题药理学第二研究室
通讯作者Liu, Jing-Gen
作者单位1.Nanjing Univ Chinese Med, Sch Pharm, Nanjing, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai 200031, Peoples R China;
3.Chinese Acad Sci, Collaborat Innovat Ctr Brain Sci, Shanghai, Peoples R China;
推荐引用方式
GB/T 7714		 Zhang, Le-Sha,Wang, Yu-Jun,Ju, Yun-Yue,et al. Role for engagement of-arrestin2 by the transactivated EGFR in agonist-specific regulation of receptor activation of ERK1/2[J]. BRITISH JOURNAL OF PHARMACOLOGY,2015,172(20):4847-4863.
APA Zhang, Le-Sha.,Wang, Yu-Jun.,Ju, Yun-Yue.,Zan, Gui-Ying.,Xu, Chi.,...&Liu, Jing-Gen.(2015).Role for engagement of-arrestin2 by the transactivated EGFR in agonist-specific regulation of receptor activation of ERK1/2.BRITISH JOURNAL OF PHARMACOLOGY,172(20),4847-4863.
MLA Zhang, Le-Sha,et al."Role for engagement of-arrestin2 by the transactivated EGFR in agonist-specific regulation of receptor activation of ERK1/2".BRITISH JOURNAL OF PHARMACOLOGY 172.20(2015):4847-4863.

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来源：上海药物研究所

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