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Disruption of disulfide restriction at integrin knees induces activation and ligand-independent signaling of alpha(4)beta(7)
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
2013-11-01
DOI10.1242/jcs.134528
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
关键词[WOS]CRYSTAL-STRUCTURE ; STRUCTURAL BASIS ; OUTSIDE-IN ; ALPHA-V-BETA-3 ; ADHESION ; DOMAINS ; ECTODOMAIN ; AFFINITY ; RECEPTOR ; ANTIBODY
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.
语种英语
WOS记录号WOS:000326392500022
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文献类型期刊论文
条目标识符http://cas-ir.dicp.ac.cn/handle/321008/137642
专题中国科学院大连化学物理研究所
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
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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.
APA Zhang, Kun.,Pan, YouDong.,Qi, JunPeng.,Yue, Jiao.,Zhang, MingBo.,...&Chen, JianFeng.(2013).Disruption of disulfide restriction at integrin knees induces activation and ligand-independent signaling of alpha(4)beta(7).JOURNAL OF CELL SCIENCE,126(21),5030-5041.
MLA Zhang, Kun,et al."Disruption of disulfide restriction at integrin knees induces activation and ligand-independent signaling of alpha(4)beta(7)".JOURNAL OF CELL SCIENCE 126.21(2013):5030-5041.
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