Inhibition of cell migration by Abl family tyrosine kinases through uncoupling of Crk-CAS complexes
Inhibition of cell migration by Abl family tyrosine kinases through uncoupling of Crk-CAS complexes
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DOI：
10.1074/jbc.m100095200
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发表时间：
2001-05-11
影响因子：
4.8
通讯作者：
Klemke, RL
中科院分区：
文献类型：
--
作者：
Kain, KH;Klemke, RL
c-Abl和c-abl相关基因产物（Arg）是非受体酪氨酸激酶，其通过与F-肌动蛋白直接结合并定位于焦点接触来调节细胞的肌动蛋白细胞骨架。然而，这种相互作用的生物学意义尚不清楚。我们在这里表明，转染COS-7细胞与激酶失活形式的c-Abl（Abl）促进c-Crk II/p130（CAS）（Crk-CAS）耦合，增强细胞迁移。此外，从缺乏内源性Abl和Arg（abl-/- Arg-/-）的小鼠中分离的胚胎成纤维细胞表现出Crk-CAS偶联和运动性增加。相反，激酶活性形式的Abl的表达或用野生型Abl重建abl-/- arg-/-细胞阻止Crk-CAS偶联并抑制细胞迁移。因此，Abl和Arg激酶通过调节细胞运动所必需的Crk和CAS衔接蛋白复合物在防止细胞迁移中起关键作用。
c-Abl and the Abl-related gene product (Arg) are nonreceptor tyrosine kinases that regulate the actin cytoskeleton of cells by direct association with F-actin and localization to focal contacts. However, the biological significance of this interaction is not known. We show here that transfection of COS-7 cells with a kinase-inactive form of c-Abl (Abl) promotes c-Crk II/p130(CAS) (Crk-CAS) coupling, enhancing cell migration. Moreover, embryonic fibroblast cells isolated from mice devoid of endogenous Abl and Arg (abl-/- arg-/-) demonstrate increased Crk-CAS coupling and motility. Conversely, expression of a kinase-active form of Abl or reconstitution of abl-/- arg-/- cells with wild-type Abl prevents Crk-CAS coupling and inhibits cell migration. Thus, Abl and Arg kinases play a critical role in preventing cell migration through regulation of Crk and CAS adaptor protein complexes, which are necessary for cell movement.