Disruption of disulfide restriction at integrin knees induces activation and ligand-independent signaling of 47
Disruption of disulfide restriction at integrin knees induces activation and ligand-independent signaling of 47
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DOI：
10.1242/jcs.134528
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发表时间：
2013-11
影响因子：
4
通讯作者：
Kun Zhang;Youdong Pan;Junpeng Qi;J. Yue;Ming-bo Zhang;Chenqi Xu;Guohui Li;JianFeng Chen
中科院分区：
文献类型：
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作者：
Kun Zhang;Youdong Pan;Junpeng Qi;J. Yue;Ming-bo Zhang;Chenqi Xu;Guohui Li;JianFeng Chen
Summary 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 4C589–C594 and 7C494–C526 activated 47. This activated integrin had a unique structure that was different from the typical extended conformation of active integrin. In addition, these activated 47 integrins spontaneously clustered on the cell membrane and triggered integrin downstream signaling independent of ligand binding. Although these disulfide bonds were not broken during 47 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.
