Serine 363 of the delta-opioid receptor is crucial for adopting distinct pathways to activate ERK1/2 in response to stimulation with different ligands

doi:10.1242/jcs.073742

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	Serine 363 of the delta-opioid receptor is crucial for adopting distinct pathways to activate ERK1/2 in response to stimulation with different ligands
	Xu, Chi 1; Hong, Min-Hua 1; Zhang, Le-Sha 1; Hou, Yuan-Yuan 1; Wang, Yu-Hua 1; Wang, Fei-Fei 2,3,4; Chen, Yue-Jun 2,3,4; Xu, Xue-Jun 1; Chen, Jie 1; Xie, Xin5
刊名	JOURNAL OF CELL SCIENCE
	2010-12-15
卷号	123 期号:24 页码:4259-4270
关键词	beta-arrestins GPCR GRK ERK delta-opioid receptor Serine 363 phosphorylation
ISSN号	0021-9533
DOI	10.1242/jcs.073742
文献子类	Article
英文摘要	Distinct opioid receptor agonists have been proved to induce differential patterns of ERK activation, but the underlying mechanisms remain unclear. Here, we report that Ser363 in the delta-opioid receptor (delta OR) determines the different abilities of the delta OR agonists DPDPE and TIPP to activate ERK by G-protein-or beta-arrestin-dependent pathways. Although both DPDPE and TIPP activated ERK1/2, they showed different temporal, spatial and desensitization patterns of ERK activation. We show that that DPDPE employed G protein as the primary mediator to activate the ERK cascade in an Src-dependent manner, whereas TIPP mainly adopted a beta-arrestin1/2-mediated pathway. Moreover, we found that DPDPE gained the capacity to adopt the beta-arrestin1/2-mediated pathway upon Ser363 mutation, accompanied by the same pattern of ERK activation as that induced by TIPP. Additionally, we found that TIPP-but not DPDPE-activated ERK could phosphorylate G-protein-coupled receptor kinase-2 and beta-arrestin1. However, such functional differences of ERK disappeared with the mutation of Ser363. Therefore, the present study reveals a crucial role for Ser363 in agonist-specific regulation of ERK activation patterns and functions.
资助项目	Ministry of Science and Technology of China[2008BAI49B05] ; Ministry of Science and Technology of China[2009CB522000] ; Ministry of Science and Technology of China[2009ZX09301-001] ; National Natural Science Foundation of China[30425002] ; National Natural Science Foundation[30873050] ; Chinese Academy of Sciences[KSCX2-YW-R-253]
WOS关键词	SIGNAL-REGULATED KINASES ; PROTEIN-COUPLED RECEPTORS ; BETA-ARRESTIN ; ADRENERGIC-RECEPTOR ; ADENYLYL-CYCLASE ; INTERNALIZATION ; MU ; DESENSITIZATION ; BETA-ARRESTIN1 ; ENDOCYTOSIS
WOS研究方向	Cell Biology
语种	英语
出版者	COMPANY BIOLOGISTS LTD
WOS记录号	WOS:000284837100008
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278689]
专题	药理学第二研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Liu, Jing-Gen
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Fudan Univ, Shanghai Med Coll, State Key Lab Med Neurobiol, Shanghai 200032, Peoples R China; 3.Fudan Univ, Shanghai Med Coll, Pharmacol Res Ctr, Shanghai 200032, Peoples R China; 4.Fudan Univ, Inst Neurobiol, Shanghai 200032, Peoples R China; 5.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 201203, Peoples R China
推荐引用方式 GB/T 7714	Xu, Chi,Hong, Min-Hua,Zhang, Le-Sha,et al. Serine 363 of the delta-opioid receptor is crucial for adopting distinct pathways to activate ERK1/2 in response to stimulation with different ligands[J]. JOURNAL OF CELL SCIENCE,2010,123(24):4259-4270.
APA	Xu, Chi.,Hong, Min-Hua.,Zhang, Le-Sha.,Hou, Yuan-Yuan.,Wang, Yu-Hua.,...&Liu, Jing-Gen.(2010).Serine 363 of the delta-opioid receptor is crucial for adopting distinct pathways to activate ERK1/2 in response to stimulation with different ligands.JOURNAL OF CELL SCIENCE,123(24),4259-4270.
MLA	Xu, Chi,et al."Serine 363 of the delta-opioid receptor is crucial for adopting distinct pathways to activate ERK1/2 in response to stimulation with different ligands".JOURNAL OF CELL SCIENCE 123.24(2010):4259-4270.