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Role of Src in ligand-specific regulation of delta-opioid receptor desensitization and internalization

文献类型：期刊论文

作者Hong, Min-Hua1; Xu, Chi1; Wang, Yu-Jun1; Ji, Jing-Li1; Tao, Yi-Min1; Xu, Xue-Jun1; Chen, Jie1; Xie, Xin2; Chi, Zhi-Qiang1; Liu, Jing-Gen1
刊名JOURNAL OF NEUROCHEMISTRY
出版日期2009-01
卷号108期号:1页码:102-114
关键词beta-arrestin delta-opioid receptor desensitization GRK2 internalization Src
ISSN号0022-3042
DOI10.1111/j.1471-4159.2008.05740.x
文献子类Article
英文摘要The opioid receptors are a member of G protein-coupled receptors that mediate physiological effects of endogenous opioid peptides and structurally distinct opioid alkaloids. Although it is well characterized that there is differential receptor desensitization and internalization properties following activation by distinct agonists, the underlying mechanisms remain elusive. We investigated the signaling events of delta-opioid receptor (delta OR) initiated by two ligands, DPDPE and TIPP. We found that although both ligands inhibited adenylyl cyclase (AC) and activated ERK1/2, only DPDPE induced desensitization and internalization of the delta OR. We further found that DPDPE, instead of TIPP, could activate GRK2 by phosphorylating the non-receptor tyrosine kinase Src and translocating it to membrane receptors. Activation of GRK2 led to the phosphorylation of serine residues in the C-terminal tail, which facilitates beta-arrestin1/2 membrane translocation. Meanwhile, we also found that DPDPE promoted beta-arrestin1 dephosphorylation in a Src-dependent manner. Thus, DPDPE appears to strengthen beta-arrestin function by dual regulations: promoting beta-arrestin recruitment and increasing beta-arrestin dephosphorylation at the plasma membrane in a Src-dependent manner. All effects initiated by DPDPE could be abolished or suppressed by PP2, an inhibitor of Src. Morphine, which has been previously shown to be unable to desensitize or internalize delta OR, also behaved as TIPP in failure to utilize Src to regulate delta OR signaling. These findings point to the existence of agonist-specific utilization of Src to regulate delta OR signaling and reveal the molecular events by which Src modulates delta OR responsiveness.
WOS关键词ACTIVATED PROTEIN-KINASE ; AGONIST-MEDIATED INTERNALIZATION ; BETA-ADRENERGIC-RECEPTOR ; BETA(2)-ADRENERGIC RECEPTOR ; TYROSINE KINASE ; COUPLED RECEPTORS ; MU ; PHOSPHORYLATION ; ENDOCYTOSIS ; RESENSITIZATION
资助项目Ministry of Science and Technology of China[G2003CB515400] ; Ministry of Science and Technology of China[2007CB935804] ; National Natural Science Foundation of China[30425002] ; Chinese Academy of Sciences[KSCXI/YW/R/68]
WOS研究方向Biochemistry & Molecular Biology ; Neurosciences & Neurology
语种英语
WOS记录号WOS:000261441500010
出版者WILEY
源URL[http://119.78.100.183/handle/2S10ELR8/279396]  
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 200031, Peoples R China;
2.Chinese Acad Sci, Shanghai Inst Mat Med, Natl Ctr Drug Screening, Shanghai 200031, Peoples R China
推荐引用方式
GB/T 7714		 Hong, Min-Hua,Xu, Chi,Wang, Yu-Jun,et al. Role of Src in ligand-specific regulation of delta-opioid receptor desensitization and internalization[J]. JOURNAL OF NEUROCHEMISTRY,2009,108(1):102-114.
APA Hong, Min-Hua.,Xu, Chi.,Wang, Yu-Jun.,Ji, Jing-Li.,Tao, Yi-Min.,...&Liu, Jing-Gen.(2009).Role of Src in ligand-specific regulation of delta-opioid receptor desensitization and internalization.JOURNAL OF NEUROCHEMISTRY,108(1),102-114.
MLA Hong, Min-Hua,et al."Role of Src in ligand-specific regulation of delta-opioid receptor desensitization and internalization".JOURNAL OF NEUROCHEMISTRY 108.1(2009):102-114.

入库方式： OAI收割

来源：上海药物研究所

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