beta-arrestin2 is critically involved in CXCR4-mediated chemotaxis, and this is mediated by its enhancement of p38 MAPK activation

	beta-arrestin2 is critically involved in CXCR4-mediated chemotaxis, and this is mediated by its enhancement of p38 MAPK activation
	Sun, Y; Cheng, ZJ; Ma, L; Pei, G
刊名	JOURNAL OF BIOLOGICAL CHEMISTRY
	2002
卷号	277 期号:51 页码:49212-49219
通讯作者	Pei, G (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Lab Mol Cell Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,
英文摘要	Chemotaxis mediated by chemokine receptors such as CXCR4 plays a key role in lymphocyte homing and hematopoiesis as well as in breast cancer metastasis. We have demonstrated previously that beta-arrestin2 functions to attenuate CXCR4-mediated G protein activation and to enhance CXCR4 internalization. Here we show further that the expression of beta-arrestin2 in both HeLa and human embryonic kidney 293 cells significantly enhances the chemotactic efficacy of stromal cell-derived factor 1alpha, the specific agonist of CXCR4, whereas the suppression of beta-arrestin2 endogenous expression by antisense or RNA-mediated interference technology considerably attenuates stromal cell-derived factor 1alpha-induced cell migration. Expression of beta-arrestin2 also augmented chemokine receptor CCR5-mediated but not epidermal growth factor receptor-mediated chemotaxis, indicating the specific effect of beta-arrestin2. Further analysis reveals that expression of beta-arrestin2 strengthened CXCR4-mediated activation of both p38 MAPK and ERK, and the suppression of beta-arrestin2 expression blocked the activation of two kinases. Interestingly, inhibition of p38 MAPK activation (but not ERK activation) by its inhibitors or by expression of a dominant-negative mutant of p38 MAPK effectively blocked the chemotactic effect of beta-arrestin2. Expression of a dominant-negative mutant of ASK1 also exerted the similar blocking effect. The results of our study suggest that beta-arrestin2 can function not only as a regulator of CXCR4 signaling but also as a mediator of stromal cell-derived factor la-induced chemotaxis and that this activity probably occurs via the ASK1/p38 MAPK pathway.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	PROTEIN-COUPLED RECEPTOR ; DOUBLE-STRANDED-RNA ; CHEMOKINE RECEPTORS ; BETA-ARRESTIN ; LYMPHOCYTE CHEMOATTRACTANT ; KINASE ACTIVATION ; MICE LACKING ; CXCR4 ; CELLS ; SDF-1
收录类别	SCI
语种	英语
WOS记录号	WOS:000180028900015
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/2551]
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	Sun, Y,Cheng, ZJ,Ma, L,et al. beta-arrestin2 is critically involved in CXCR4-mediated chemotaxis, and this is mediated by its enhancement of p38 MAPK activation[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2002,277(51):49212-49219.
APA	Sun, Y,Cheng, ZJ,Ma, L,&Pei, G.(2002).beta-arrestin2 is critically involved in CXCR4-mediated chemotaxis, and this is mediated by its enhancement of p38 MAPK activation.JOURNAL OF BIOLOGICAL CHEMISTRY,277(51),49212-49219.
MLA	Sun, Y,et al."beta-arrestin2 is critically involved in CXCR4-mediated chemotaxis, and this is mediated by its enhancement of p38 MAPK activation".JOURNAL OF BIOLOGICAL CHEMISTRY 277.51(2002):49212-49219.