Inhibition of cell migration by Abl family tyrosine kinases through uncoupling of Crk-CAS complexes.
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.
Kain
K H
KH
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
Klemke
R L
RL
D000818:Animals; D019556:COS Cells; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002522:Chlorocebus aethiops; D050719:Crk-Associated Substrate Protein; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D016313:Genes, abl; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D011506:Proteins; D011518:Proto-Oncogene Proteins; D016315:Proto-Oncogene Proteins c-abl / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D050737:Proto-Oncogene Proteins c-crk; D016160:Retinoblastoma Protein / Q000378:metabolism; D050717:Retinoblastoma-Like Protein p130; D014162:Transfection; D018909:src Homology Domains
C493842:Bcar1 protein, mouse; D050719:Crk-Associated Substrate Protein; D007328:Insulin; D010750:Phosphoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D050737:Proto-Oncogene Proteins c-crk; D016160:Retinoblastoma Protein; D050717:Retinoblastoma-Like Protein p130; D011494:Protein Kinases; D016315:Proto-Oncogene Proteins c-abl