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, Chi1; Hong, Min-Hua1; Zhang, Le-Sha1; Hou, Yuan-Yuan1; Wang, Yu-Hua1; Wang, Fei-Fei2,3,4; Chen, Yue-Jun2,3,4; Xu, Xue-Jun1; Chen, Jie1; Xie, Xin5![]() | |
刊名 | JOURNAL OF CELL SCIENCE
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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. |
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