Selective regulation of integrin-cytoskeleton interactions by the tyrosine kinase Src
Selective regulation of integrin-cytoskeleton interactions by the tyrosine kinase Src
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DOI：
10.1038/12021
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发表时间：
1999-08-01
影响因子：
21.3
通讯作者：
Sheetz, MP
中科院分区：
文献类型：
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作者：
Felsenfeld, DP;Schwartzberg, PL;Sheetz, MP
细胞在细胞外基质（ECM）底物上的运动依赖于通过称为整合素的黏附受体对底物产生的受调节的力。在此我们表明，整合素介导的牵引力可被酪氨酸激酶Src选择性调节。在Src缺陷的成纤维细胞中，细胞在ECM成分玻连蛋白上的铺展受到抑制，而整合素玻连蛋白受体与产生力的细胞骨架之间的连接对底物刚性的响应增强作用却显著增加。相反，Src缺乏对纤连蛋白受体功能没有可检测到的影响。最后，截短的Src（缺失激酶结构域）与α(v)而非β(1)整合素共定位在黏着斑位点。这些数据与Src和玻连蛋白受体之间在整合素 - 细胞骨架界面起作用以调节细胞铺展和迁移的选择性功能相互作用是一致的。
Cell motility on extracellular-matrix (ECM) substrates depends on the regulated generation of force against the substrate through adhesion receptors known as integrins, Here we show that integrin-mediated traction forces can be selectively modulated by the tyrosine kinase Src, In Src-deficient fibroblasts, cell spreading on the ECM component vitronectin is inhibited, while the strengthening of linkages between integrin vitronectin receptors and the force-generating cytoskeleton in response to substrate rigidity is dramatically increased. In contrast, Src deficiency has no detectable effects on fibronectin-receptor function. Finally, truncated Src (lacking the kinase domain) co-localizes to focal-adhesion sites with alpha(v) but not with beta(1) integrins, These data are consistent with a selective, functional interaction between Src and the vitronectin receptor that acts at the integrin-cytoskeleton interface to regulate cell spreading and migration.