Disruption of disulfide restriction at integrin knees induces activation and ligand-independent signaling of alpha(4)beta(7)

	Disruption of disulfide restriction at integrin knees induces activation and ligand-independent signaling of alpha(4)beta(7)
	Zhang, Kun 1; Pan, YouDong 1; Qi, JunPeng 1; Yue, Jiao 1; Zhang, MingBo 2,3; Xu, ChenQi 1; Li, GuoHui 2; Chen, JianFeng 1
刊名	journal of cell science
	2013-11-01
卷号	126 期号:21 页码:5030-5041
关键词	Disulfide-restriction Integrin clustering Ligand-independent signaling
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.
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
收录类别	SCI
语种	英语
WOS记录号	WOS:000326392500022
公开日期	2015-11-10
内容类型	期刊论文
源URL	[http://159.226.238.44/handle/321008/137642]
专题	大连化学物理研究所_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
推荐引用方式 GB/T 7714	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.