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Inhibition of Cell Migration by Abl Family Tyrosine Kinases through Uncoupling of Crk-CAS Complexes

descriptionPublicationkeyboard_double_arrow_right Article 01 May 2001 English Publisher:Elsevier BVJournal:Journal of Biological Chemistry, volume 276, pages 16,185-16,192 (issn: 0021-9258,

Authors: Kristin H. Kain; Richard L. Klemke;

doi: 10.1074/jbc.m100095200

pmid: 11279004

Inhibition of Cell Migration by Abl Family Tyrosine Kinases through Uncoupling of Crk-CAS Complexes

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Abstract

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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Scripps Research Institute
United States

Keywords

Mice, Knockout, Retinoblastoma-Like Protein p130, Proteins, Fibroblasts, Genes, abl, Proto-Oncogene Proteins c-crk, Embryo, Mammalian, Phosphoproteins, Transfection, Retinoblastoma Protein, Mice, Crk-Associated Substrate Protein, Cell Movement, Proto-Oncogene Proteins, COS Cells, Chlorocebus aethiops, Animals, Insulin, Proto-Oncogene Proteins c-abl, Protein Kinases

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