DICP OpenIR
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
KeywordDisulfide-restriction Integrin Clustering Ligand-independent Signaling
Source PublicationJOURNAL OF CELL SCIENCE
2013-11-01
DOI10.1242/jcs.134528
Volume126Issue:21Pages:5030-5041
Indexed BySCI
SubtypeArticle
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
WOS SubjectCell Biology
WOS Research AreaCell Biology
WOS KeywordCRYSTAL-STRUCTURE ; STRUCTURAL BASIS ; OUTSIDE-IN ; ALPHA-V-BETA-3 ; ADHESION ; DOMAINS ; ECTODOMAIN ; AFFINITY ; RECEPTOR ; ANTIBODY
AbstractControl 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.
Language英语
WOS IDWOS:000326392500022
Citation statistics
Cited Times:3[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://cas-ir.dicp.ac.cn/handle/321008/137642
Collection中国科学院大连化学物理研究所
Affiliation1.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
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.
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