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学科主题: 基础医学
题名:
BMP4 Signaling Acts via Dual-Specificity Phosphatase 9 to Control ERK Activity in Mouse Embryonic Stem Cells
作者: Li, Zhongwei1; Fei, Teng1; Zhang, Jianping1; Zhu, Gaoyang1; Wang, Lu1; Lu, Danyu2; Chi, Xiaochun2; Teng, Yan3; Hou, Ning3; Yang, Xiao3; Zhang, Hongquan2; Han, Jing-Dong J.4; Chen, Ye-Guang1
刊名: CELL STEM CELL
发表日期: 2012-02-03
DOI: 10.1016/j.stem.2011.12.016
卷: 10, 期:2, 页:171-182
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Cell & Tissue Engineering ; Cell Biology
研究领域[WOS]: Cell Biology
关键词[WOS]: ACTIVATED PROTEIN-KINASE ; SELF-RENEWAL ; TRANSCRIPTIONAL NETWORK ; MAP KINASE ; DIFFERENTIATION ; PLURIPOTENCY ; PATHWAYS ; TROPHOBLAST ; MAINTENANCE ; INVOLVEMENT
英文摘要:

Extrinsic BMP and LIF signaling collaboratively maintain mouse embryonic stem cell (ESC) pluripotency, whereas appropriate ERK activity is essential for ESC fate commitment. However, how the extrinsic signals restrain appropriate ERK activity remains elusive. Here, we show that, whereas LIF sustains relatively high ERK activity, BMP4 can steadily attenuate ERK activity by upregulating ERK-specific dual-specificity phosphatase 9 (DUSP9). This upregulation requires Smad1/5 and Smad4 and specifically occurs to DUSP9, but not other DUSPs, and only in ESCs. Through DUSP9-mediated inhibition of ERK activity, BMP signaling reinforces the self-renewal status of mouse ESCs together with LIF. Upon LIF withdrawal, ESCs spontaneously undergo neural differentiation, during which process DUSP9 can partially mediate BMP inhibition on neural commitment. Collectively, our findings identify DUSP9 as a critical mediator of BMP signaling to control appropriate ERK activity critical for ESC fate determination.

语种: 英语
所属项目编号: 2011CBA01104 ; 2011CB943803 ; 2010CB833706 ; 30921004 ; 91019003 ; 30930050 ; 2010THZ0
项目资助者: Ministry of Sciences and Technology of China ; National Natural Science Foundation of China ; Tsinghua University
WOS记录号: WOS:000300272100010
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57867
Appears in Collections:基础医学院_期刊论文

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作者单位: 1.Tsinghua Univ, Sch Life Sci, Tsinghua Peking Ctr Life Sci, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China
2.Peking Univ, Sch Basic Med Sci, Lab Stem Cells Dev & Reprod Med, Beijing 100191, Peoples R China
3.Inst Biotechnol, Genet Lab Dev & Dis, State Key Lab Prote, Beijing 100071, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Biol Sci, Max Planck Partner Inst Computat Biol, Shanghai 200031, Peoples R China

Recommended Citation:
Li, Zhongwei,Fei, Teng,Zhang, Jianping,et al. BMP4 Signaling Acts via Dual-Specificity Phosphatase 9 to Control ERK Activity in Mouse Embryonic Stem Cells[J]. CELL STEM CELL,2012,10(2):171-182.
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