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学科主题: 基础医学
题名:
ERK-MAPK Drives Lamellipodia Protrusion by Activating the WAVE2 Regulatory Complex
作者: Mendoza, Michelle C.1; Er, E. Emrah1; Zhang, Wenjuan2; Ballif, Bryan A.3,4; Elliott, Hunter L.1,5; Danuser, Gaudenz1; Blenis, John1
刊名: MOLECULAR CELL
发表日期: 2011-03-18
DOI: 10.1016/j.molcel.2011.02.031
卷: 41, 期:6, 页:661-671
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]: PROTEIN-KINASE ; CELL MOTILITY ; GROWTH-FACTOR ; PAXILLIN PHOSPHORYLATION ; ACTIN POLYMERIZATION ; MYOSIN-II ; IN-VIVO ; ADHESION ; MEMBRANE ; DYNAMICS
英文摘要:

Cell movement begins with a leading edge protrusion, which is stabilized by nascent adhesions and retracted by mature adhesions. The ERK-MAPK (extracellular signal-regulated kinase-mitogen-activated protein kinase) localizes to protrusions and adhesions, but how it regulates motility is not understood. We demonstrate that ERK controls protrusion initiation and protrusion speed. Lamellipodial protrusions are generated via the WRC (WAVE2 regulatory complex), which activates the Arp2/3 actin nucleator for actin assembly. The WRC must be phosphorylated to be activated, but the sites and kinases that regulate its intermolecular changes and membrane recruitment are unknown. We show that ERK colocalizes with the WRC at lamellipodial leading edges and directly phosphorylates two WRC components: WAVE2 and Abil. The, phosphorylations are required for functional WRC interaction with Arp2/3 and actin during cell protrusion. Thus, ERK coordinates adhesion disassembly with WRC activation and actin polymerization to promote productive leading edge advancement during cell migration.

语种: 英语
所属项目编号: R37CA46595 ; P20 RR16462 ; U54GM64346
项目资助者: NCI ; Susan G. Komen PDF ; Vermont Genetics Network through NIH, NCRR ; NIH
WOS记录号: WOS:000288827500007
Citation statistics:
内容类型: 期刊论文
版本: 出版稿
URI标识: http://ir.bjmu.edu.cn/handle/400002259/63785
Appears in Collections:基础医学院_北京大学人类疾病基因研究中心_期刊论文

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作者单位: 1.Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA
2.Univ Vermont, Dept Biol, Burlington, VT 05405 USA
3.Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA
4.Peking Univ, Ctr Human Dis Genom, Dept Immunol, Beijing 100191, Peoples R China
5.Univ Vermont, Vermont Genet Network Prote Facil, Burlington, VT 05405 USA

Recommended Citation:
Mendoza, Michelle C.,Er, E. Emrah,Zhang, Wenjuan,et al. ERK-MAPK Drives Lamellipodia Protrusion by Activating the WAVE2 Regulatory Complex[J]. MOLECULAR CELL,2011,41(6):661-671.
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