Heterologous activation of protein kinase C stimulates phosphorylation of delta-opioid receptor at Serine 344, resulting in beta-arrestin- and clathrin-mediated receptor internalization

	Heterologous activation of protein kinase C stimulates phosphorylation of delta-opioid receptor at Serine 344, resulting in beta-arrestin- and clathrin-mediated receptor internalization
	Xiang, B; Yu, GH; Guo, J; Chen, L; Hu, W; Pei, G; Ma, L
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2001
卷号	276 期号:7 页码:4709-4716
通讯作者	Ma, L (reprint author), Fudan Univ, Med Ctr, Natl Lab Med Neurobiol, 138 Yi Xue Yuan Rd, Shanghai 200032, Peoples R China.,
英文摘要	The purpose of the current study is to investigate the effect of opioid-independent, heterologous activation of protein kinase C (PKC) on the responsiveness of opioid receptor and the underlying molecular mechanisms. Our result showed that removing the C terminus of delta opioid receptor (DOR) containing six Ser/Thr residues abolished both DPDPE- and phorbol 12-myristate 13-acetate (PMA)-induced DOR phosphorylation. The phosphorylation levels of DOR mutants T352A, T353A, and T358A/T361A/S363S were comparable to that of the wildtype DOR, whereas S344G substitution blocked PMA-induced receptor phosphorylation, indicating that PKC-mediated phosphorylation occurs at Ser-344. PKC-mediated Ser-344 phosphorylation was also induced by activation of G(q)-coupled alpha (1A)-adrenergic receptor or increase in intracellular Ca2+ concentration. Activation of PKC by PMA, alpha (1A)-adrenergic receptor agonist, and ionomycin resulted in DOE internalization that required phosphorylation of Ser-344, Expression of dominant negative p-arrestin and hypertonic sucrose treatment blocked PMA-induced DOR internalization, suggesting that PKC mediates DOR internalization via a beta -arrestin- and clathrin-dependent mechanism. Further study demonstrated that agonist-dependent G protein-coupled receptor kinase (GRK) phosphorylation sites in DOR are not targets of PKC. Agonist-dependent, GRK-mediated receptor phosphorylation and agonist-independent, PKC-mediated DOR phosphorylation were additive, but agonist-induced receptor phosphorylation could inhibit PKC-catalyzed heterologous DOR phosphorylation and subsequent internalization. These data demonstrate that the responsiveness of opioid receptor is regulated by both PKC and GRK through agonist-dependent and agonist-independent mechanisms and PKC-mediated receptor phosphorylation is an important molecular mechanism of heterologous regulation of opioid receptor functions.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	ADENYLYL-CYCLASE ; OPIATE RECEPTOR ; XENOPUS OOCYTES ; PHORBOL ESTERS ; AGONIST ; DESENSITIZATION ; MORPHINE ; ANTINOCICEPTION ; TOLERANCE ; KAPPA
收录类别	SCI
语种	英语
WOS记录号	WOS:000168484300026
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/2697]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Xiang, B,Yu, GH,Guo, J,et al. Heterologous activation of protein kinase C stimulates phosphorylation of delta-opioid receptor at Serine 344, resulting in beta-arrestin- and clathrin-mediated receptor internalization[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2001,276(7):4709-4716.
APA	Xiang, B.,Yu, GH.,Guo, J.,Chen, L.,Hu, W.,...&Ma, L.(2001).Heterologous activation of protein kinase C stimulates phosphorylation of delta-opioid receptor at Serine 344, resulting in beta-arrestin- and clathrin-mediated receptor internalization.JOURNAL OF BIOLOGICAL CHEMISTRY,276(7),4709-4716.
MLA	Xiang, B,et al."Heterologous activation of protein kinase C stimulates phosphorylation of delta-opioid receptor at Serine 344, resulting in beta-arrestin- and clathrin-mediated receptor internalization".JOURNAL OF BIOLOGICAL CHEMISTRY 276.7(2001):4709-4716.