Subcellular localization of beta-arrestins is determined by their intact N domain and the nuclear export signal at the C terminus

	Subcellular localization of beta-arrestins is determined by their intact N domain and the nuclear export signal at the C terminus
	Wang, P; Wu, YL; Ge, X; Ma, L; Pei, G
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2003
卷号	278 期号:13 页码:11648-11653
通讯作者	Pei, G (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Mol Cell Biol Lab, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,
英文摘要	beta-Arrestinl and beta-arrestin2 play a key role in the regulation of G protein-coupled receptor-mediated signaling, whereas the subcellular distribution of beta-arrestin1 and beta-arrestin2 has been shown to be quite different. In this study, we found that although both beta-arrestin1 and beta-arrestin2 are able to interact with ubiquitin-protein isopeptide ligase (E3) Mdm2, only expression of beta-arrestin2 leads to the relocalization of Mdm2 from the nucleus to the cytoplasm. Further study reveals that beta-arrestin2 but not beta-arrestin1 shuttles between the cytoplasm and nucleus in a leptomycin B-sensitive manner. A hydrophobic amino acid-rich region (VXXX-LXL) at the C terminus of beta-arrestin2 was further demonstrated to serve as a nuclear export signal responsible for the extranuclear localization of beta-arrestin2. In the corresponding region of beta-arrestin1, there is a single amino acid difference (Glu instead of Leu. in beta-arrestin2), and mutation of Glu to Leu conferred to beta-arrestin1 similar subcellular distribution to that of beta-arrestin2. Moreover, data from a series of deletion mutations demonstrated that the N domain (residues 1-185) was indispensable for the nuclear localization of both beta-arrestins, and the results from a Val to Asp point mutation in the N domain also supported this notion. In addition, our data showed that nucleocytoplasmic shuttling of beta-arrestin2 was required, via protein/protein interaction, for the cytoplasmic relocalization of Mdm2 and JNK3, another well known beta-arrestin2-binding protein. Our study thus suggests that both the nuclear export signal motif and the N domain of beta-arrestins are critical for the regulation of their subeellular localization and that beta-arrestin2 may modulate the function of its binding partners such as Mdm2 and JNK3 by alteration of their subcellular distribution.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	PROTEIN-COUPLED RECEPTORS ; PROSTAGLANDIN E-2 RECEPTORS ; BETA(2)-ADRENERGIC RECEPTOR ; CARBOXYL-TERMINUS ; MOLECULAR-CLONING ; CRYSTAL-STRUCTURE ; CLATHRIN ADAPTER ; VISUAL ARRESTIN ; BINDING ; BETA-ARRESTIN2
收录类别	SCI
语种	英语
WOS记录号	WOS:000181855400098
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/2373]
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	Wang, P,Wu, YL,Ge, X,et al. Subcellular localization of beta-arrestins is determined by their intact N domain and the nuclear export signal at the C terminus[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2003,278(13):11648-11653.
APA	Wang, P,Wu, YL,Ge, X,Ma, L,&Pei, G.(2003).Subcellular localization of beta-arrestins is determined by their intact N domain and the nuclear export signal at the C terminus.JOURNAL OF BIOLOGICAL CHEMISTRY,278(13),11648-11653.
MLA	Wang, P,et al."Subcellular localization of beta-arrestins is determined by their intact N domain and the nuclear export signal at the C terminus".JOURNAL OF BIOLOGICAL CHEMISTRY 278.13(2003):11648-11653.