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J. Biol. Chem., Vol. 276, Issue 19, 16185-16192, May 11, 2001
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From the Department of Immunology, The Scripps Research Institute,
La Jolla, California 92037
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/p130CAS (Crk-CAS) coupling, enhancing cell
migration. Moreover, embryonic fibroblast cells isolated from mice
devoid of endogenous Abl and Arg (abl
Inhibition of Cell Migration by Abl Family Tyrosine
Kinases through Uncoupling of Crk-CAS Complexes*
/
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.
*
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Immunology,
CAL-9, The Scripps Research Institute, 10550 North Torrey Pines Rd., La
Jolla, CA 92037. Tel.: 858-784-7750; Fax: 858-784-7785; E-mail:
klemke@scripps.edu.
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