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A Novel Protein Kinase A-independent, beta-Arrestin-1-dependent Signaling Pathway for p38 Mitogen-activated Protein Kinase Activation by beta(2)-Adrenergic Receptors
Gong, Kaizheng; Li, Zijian; Xu, Ming; Du, Jianhai; Lv, Zhizhen; Zhang, Youyi
刊名JOURNAL OF BIOLOGICAL CHEMISTRY
2008-10-24
DOI10.1074/jbc.M801313200
283期:43页:29028-29036
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology
资助者People&prime ; s Republic of China ; Natural Science Foundation of China ; People&prime ; s Republic of China ; Natural Science Foundation of China
研究领域[WOS]Biochemistry & Molecular Biology
关键词[WOS]BETA-ARRESTIN RECRUITMENT ; NF-KAPPA-B ; NADPH OXIDASE ; COUPLED RECEPTORS ; BETA-2-ADRENERGIC RECEPTOR ; CARDIAC FIBROBLASTS ; MAPK ACTIVATION ; ERK ACTIVATION ; ANGIOTENSIN-II ; PHOSPHORYLATION
英文摘要

A growing body of evidence has demonstrated that p38 mitogen-activated protein kinase (MAPK) has a crucial role in various physiological and pathological processes mediated by beta(2)-adrenergic receptors (beta(2)-ARs). However, the detailed mechanism of beta(2)-ARs-induced p38 MAPK activation has not yet been fully defined. The present study demonstrates a novel kinetic model of p38 MAPK activation induced by beta(2)-ARs in human embryonic kidney 293A cells. The beta(2)-AR agonist isoproterenol induced a time-dependent biphasic phosphorylation of p38 MAPK: the early phase peaked at 10 min, and was followed by a delayed phase that appeared at 90 min and was sustained for 6 h. Interestingly, inhibition of the cAMP/protein kinase A (PKA) pathway failed to affect the early phosphorylation but abolished the delayed activation. By contrast, silencing of beta-arrestin-1 expression by small interfering RNA inhibited the early phase activation of p38 MAPK. Furthermore, the NADPH oxidase complex is a downstream target of beta-arrestin-1, as evidenced by the fact that isoproterenol-induced Rac1 activation was also suppressed by beta-arrestin-1 knockdown. In addition, early phase activation of p38 MAPK was prevented by inactivation of Rac1 and NADPH oxidase by pharmacological inhibitors, overexpression of a dominant negative mutant of Rac1, and p47(phox) knockdown by RNA interference. Of note, we demonstrated that only early activation of p38 MAPK is involved in isoproterenol-induced F-actin rearrangement. Collectively, these data suggest that the classic cAMP/PKA pathway is responsible for the delayed activation, whereas a beta-arrestin-1/Rac1/NADPH oxidase-dependent signaling is a heretofore unrecognized mechanism for beta(2)-AR-mediated early activation of p38 MAPK.

语种英语
所属项目编号G2006CB503806 ; 30672466 ; 30570716
资助者People&prime ; s Republic of China ; Natural Science Foundation of China ; People&prime ; s Republic of China ; Natural Science Foundation of China
WOS记录号WOS:000260179900029
引用统计
被引频次:48[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/57046
专题北京大学第三临床医学院_心血管内科
作者单位1.Peking Univ, Inst Vasc Med, Hosp 3, Beijing 100191, Peoples R China
2.Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing 100191, Peoples R China
推荐引用方式
GB/T 7714
Gong, Kaizheng,Li, Zijian,Xu, Ming,et al. A Novel Protein Kinase A-independent, beta-Arrestin-1-dependent Signaling Pathway for p38 Mitogen-activated Protein Kinase Activation by beta(2)-Adrenergic Receptors[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2008,283(43):29028-29036.
APA Gong, Kaizheng,Li, Zijian,Xu, Ming,Du, Jianhai,Lv, Zhizhen,&Zhang, Youyi.(2008).A Novel Protein Kinase A-independent, beta-Arrestin-1-dependent Signaling Pathway for p38 Mitogen-activated Protein Kinase Activation by beta(2)-Adrenergic Receptors.JOURNAL OF BIOLOGICAL CHEMISTRY,283(43),29028-29036.
MLA Gong, Kaizheng,et al."A Novel Protein Kinase A-independent, beta-Arrestin-1-dependent Signaling Pathway for p38 Mitogen-activated Protein Kinase Activation by beta(2)-Adrenergic Receptors".JOURNAL OF BIOLOGICAL CHEMISTRY 283.43(2008):29028-29036.
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