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.
Department of Immunology, The Scripps Research Institute, La Jolla, California 92037, USA.
K H
KH
Kain
R L
RL
Klemke
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