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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 | |
| Keyword | Disulfide-restriction Integrin Clustering Ligand-independent Signaling |
| Source Publication | JOURNAL OF CELL SCIENCE
 |
| 2013-11-01 | |
| DOI | 10.1242/jcs.134528 |
| Volume | 126Issue:21Pages:5030-5041 |
| Indexed By | SCI |
| Subtype | Article |
| WOS Headings | Science & Technology ; Life Sciences & Biomedicine |
| WOS Subject | Cell Biology |
| WOS Research Area | Cell Biology |
| WOS Keyword | CRYSTAL-STRUCTURE ; STRUCTURAL BASIS ; OUTSIDE-IN ; ALPHA-V-BETA-3 ; ADHESION ; DOMAINS ; ECTODOMAIN ; AFFINITY ; RECEPTOR ; ANTIBODY |
| Abstract | 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. |
| Language | 英语 |
| WOS ID | WOS:000326392500022 |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://cas-ir.dicp.ac.cn/handle/321008/137642 |
| Collection | 中国科学院大连化学物理研究所 |
| Affiliation | 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 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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