Kain K H, Klemke R L
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
J Biol Chem. 2001 May 11;276(19):16185-92. doi: 10.1074/jbc.M100095200. Epub 2001 Jan 19.
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.
c-Abl和Abl相关基因产物（Arg）是非受体酪氨酸激酶，它们通过与F-肌动蛋白直接结合并定位于粘着斑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。我们在此表明，用激酶失活形式的c-Abl（Abl）转染COS-7细胞可促进c-Crk II/p130（CAS）（Crk-CAS）偶联，增强细胞迁移。此外，从小鼠中分离出的缺乏内源性Abl和Arg（abl-/- arg-/-）的胚胎成纤维细胞显示出Crk-CAS偶联增加和运动性增强。相反，Abl激酶活性形式的表达或用野生型Abl重建abl-/- arg-/-细胞可防止Crk-CAS偶联并抑制细胞迁移。因此，Abl和Arg激酶在通过调节对细胞运动至关重要的Crk和CAS衔接蛋白复合物来防止细胞迁移中起关键作用。
