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学科主题: 基础医学
题名:
Involvement of ERK-RSK cascade in phenylephrine-induced phosphorylation of GATA4
作者: Li, Tao1; Liu, Zhiqiang3; Hu, Xiaoqing2; Ma, Kangtao2; Zhou, Chunyan2
关键词: GATA4 ; ERK ; RSK ; Phosphorylation ; Cardiac hypertrophy
刊名: BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
发表日期: 2012-02-01
DOI: 10.1016/j.bbamcr.2011.12.009
卷: 1823, 期:2, 页:582-592
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Cell Biology
研究领域[WOS]: Biochemistry & Molecular Biology ; Cell Biology
关键词[WOS]: TRANSCRIPTION FACTOR GATA-4 ; ACTIVATED PROTEIN-KINASE ; COFFIN-LOWRY-SYNDROME ; HEART TUBE FORMATION ; RIBOSOMAL S6 KINASE ; SIGNALING PATHWAYS ; CARDIAC MYOCYTES ; CARDIOMYOCYTE HYPERTROPHY ; VENTRAL MORPHOGENESIS ; GENE-EXPRESSION
英文摘要:

GATA4 has been characterized as a crucial regulator of cardiac development and hypertrophy. Multiple signaling pathways involving MAPK contribute to GATA4 activation via direct phosphorylation. MSK and RSK are two kinase families mediating signal transduction downstream of the MAPK cascade. In this study, we investigated the effects of MSK and RSK on GATA4 activation. Overexpression of RSK2 greatly increased phosphorylation of GATA4 at Ser261. This phosphorylation enhanced its transcriptional and DNA binding activity. RSK-dependent phosphorylation of GATA4 also led to enhanced interaction with NKX2.5 and p300. Sequential phosphorylation of the ERK-RSK-GATA4 cascade and nuclear accumulation of RSK in cardiomyocytes were observed after phenylephrine treatment. Inhibition of RSK using the small molecule SL0101 abrogated GATA4 phosphorylation at Ser261, ultimately leading to a repression of fetal cardiac genes. Adenovirus-mediated overexpression of MSK1 had no direct effect on GATA4 phosphorylation but increased GATA4 expression. Together with GATA4 phosphorylation at Ser105 by ERK1/2, our findings show dual phosphotylation of GATA4 by the ERK-RSK cascade and suggest that MSK and RSK have distinct effects in PE-induced cardiac hypertrophic response. (C) 2011 Elsevier B.V. All rights reserved.

语种: 英语
所属项目编号: 30871253 ; 90919022 ; 31101057 ; B07001 ; ZC304009172
项目资助者: National Natural Sciences Foundation of China ; 111 Project of China ; Sciences Foundation of Zhejiang Normal University
WOS记录号: WOS:000301155700040
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52968
Appears in Collections:基础医学院_期刊论文

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作者单位: 1.Zhejiang Normal Univ, Dept Biol, Coll Chem & Life Sci, Jinhua 321004, Zhejiang, Peoples R China
2.Peking Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Beijing 100191, Peoples R China
3.Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 USA

Recommended Citation:
Li, Tao,Liu, Zhiqiang,Hu, Xiaoqing,et al. Involvement of ERK-RSK cascade in phenylephrine-induced phosphorylation of GATA4[J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH,2012,1823(2):582-592.
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