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Publication : Inhibition of cell migration by Abl family tyrosine kinases through uncoupling of Crk-CAS complexes.

First Author  Kain KH Year  2001
Journal  J Biol Chem Volume  276
Issue  19 Pages  16185-92
PubMed ID  11279004 Mgi Jnum  J:116356
Mgi Id  MGI:3694142 Doi  10.1074/jbc.M100095200
Citation  Kain KH, et al. (2001) Inhibition of cell migration by Abl family tyrosine kinases through uncoupling of Crk-CAS complexes. J Biol Chem 276(19):16185-92
abstractText  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.
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