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    J Biol Chem. 2001 May 11;276(19):16185-92. Epub 2001 Jan 19.

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

    Kain KH, Klemke RL.

    Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.

    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.

    PMID: 11279004 [PubMed - indexed for MEDLINE]

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