INTEGRIN REGULATION OF C-ABL TYROSINE KINASE-ACTIVITY AND CYTOPLASMIC-NUCLEAR TRANSPORT

The product of the c-abl protooncogene is a nonreceptor tyrosine kinas e found in both the cytoplasm and the nucleus, We report herein that c ell adhesion regulates the kinase activity and subcellular localizatio n of c-Abl. When fibroblastic cells are detached from the extracellula r matrix, kinase activity of both cytoplasmic and nuclear c-Abl decrea ses, but there is no detectable alteration in the subcellular distribu tion. 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 o f adhesion, but the nuclear c-Abl is reactivated after 30 min, correla ting closely with its return to the nucleus and suggesting that the ac tive nuclear c-Abl originates in the cytoplasm. In quiescent cells whe re nuclear c-Abl activity is low, the cytoplasmic c-Abl is similarly r egulated by adhesion but the nuclear c-Abl is not activated upon cell attachment. These results show that c-Abl activation requires cell adh esion and that this tyrosine kinase can transmit integrin signals to t he nucleus where it may function to integrate adhesion and cell cycle signals.