Integrin regulation of c-Abl tyrosine kinase activity and cytoplasmic-nuclear transport.
The product of the c-abl protooncogene is a nonreceptor tyrosine kinase found in both the cytoplasm and the nucleus. We report herein that cell adhesion regulates the kinase activity and subcellular localization of c-Abl. When fibroblastic cells are detached from the extracellular matrix, kinase activity of both cytoplasmic and nuclear c-Abl decreases, but there is no detectable alteration in the subcellular distribution. Upon adhesion to the extracellular matrix protein fibronectin, a transient recruitment of a subset of c-Abl to early focal contacts is observed coincident with the export of c-Abl from the nucleus to the cytoplasm. The cytoplasmic pool of c-Abl is reactivated within 5 min of adhesion, but the nuclear c-Abl is reactivated after 30 min, correlating closely with its return to the nucleus and suggesting that the active nuclear c-Abl originates in the cytoplasm. In quiescent cells where nuclear c-Abl activity is low, the cytoplasmic c-Abl is similarly regulated by adhesion but the nuclear c-Abl is not activated upon cell attachment. These results show that c-Abl activation requires cell adhesion and that this tyrosine kinase can transmit integrin signals to the nucleus where it may function to integrate adhesion and cell cycle signals.
Lewis
J M
JM
Department of Biology, University of California at San Diego, La Jolla 92037-0347, USA.
Baskaran
R
R
Taagepera
S
S
Schwartz
M A
MA
Wang
J Y
JY
D016475:3T3 Cells; D000818:Animals; D002448:Cell Adhesion; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005353:Fibronectins; D006706:Homeostasis; D016023:Integrins / Q000502:physiology*; D007700:Kinetics; D051379:Mice; D011107:Polylysine; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism*; D012319:RNA Polymerase II / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism
D005353:Fibronectins; D016023:Integrins; D011993:Recombinant Fusion Proteins; D011107:Polylysine; D011505:Protein-Tyrosine Kinases; D016315:Proto-Oncogene Proteins c-abl; D012319:RNA Polymerase II