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题名: Disruption of disulfide restriction at integrin knees induces activation and ligand-independent signaling of alpha(4)beta(7)
作者: Zhang, Kun1;  Pan, YouDong1;  Qi, JunPeng1;  Yue, Jiao1;  Zhang, MingBo2, 3;  Xu, ChenQi1;  Li, GuoHui2;  Chen, JianFeng1
关键词: Disulfide-restriction ;  Integrin clustering ;  Ligand-independent signaling
刊名: JOURNAL OF CELL SCIENCE
发表日期: 2013-11-01
DOI: 10.1242/jcs.134528
卷: 126, 期:21, 页:5030-5041
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology ;  Life Sciences & Biomedicine
类目[WOS]: Cell Biology
研究领域[WOS]: Cell Biology
英文摘要: Control of integrin activation and signaling plays crucial roles in cell adhesion, spreading and migration. Here, we report that selective breakage of two conserved disulfide bonds located at the knees of integrin alpha(4)C589-C594 and beta(7)C494-C526 activated alpha(4)beta(7). This activated integrin had a unique structure that was different from the typical extended conformation of active integrin. In addition, these activated alpha(4)beta(7) integrins spontaneously clustered on the cell membrane and triggered integrin downstream signaling independent of ligand binding. Although these disulfide bonds were not broken during alpha(4)beta(7) activation by inside-out signaling or Mn2+, they could be specifically reduced by 0.1 mM dithiothreitol, a reducing strength that could be produced in vivo under certain conditions. Our findings reveal a novel mechanism of integrin activation under specific reducing conditions by which integrin can signal and promote cell spreading in the absence of ligand.
关键词[WOS]: CRYSTAL-STRUCTURE ;  STRUCTURAL BASIS ;  OUTSIDE-IN ;  ALPHA-V-BETA-3 ;  ADHESION ;  DOMAINS ;  ECTODOMAIN ;  AFFINITY ;  RECEPTOR ;  ANTIBODY
语种: 英语
WOS记录号: WOS:000326392500022
Citation statistics: 
内容类型: 期刊论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/137642
Appears in Collections:中国科学院大连化学物理研究所_期刊论文

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作者单位: 1.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China
2.Chinese Acad Sci, Dalian Inst Chem Phys, State Key Lab Mol React Dynam, Lab Mol Modeling & Design, Dalian 116023, Peoples R China
3.Liaoning Univ Tradit Chinese Med, Coll Pharm, Dalian 116600, Peoples R China

Recommended Citation:
Zhang, Kun,Pan, YouDong,Qi, JunPeng,et al. Disruption of disulfide restriction at integrin knees induces activation and ligand-independent signaling of alpha(4)beta(7)[J]. JOURNAL OF CELL SCIENCE,2013,126(21):5030-5041.
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