THE NUCLEAR TYROSINE KINASE C-ABL NEGATIVELY REGULATES CELL-GROWTH

c-Abl is a tyrosine kinase localized primarily in the nucleus. Previou s assays for abl function rely on cellular transformation by abl mutan ts, which are cytoplasmic. Using a conditional overexpression strategy , we have developed a functional assay for c-abl. Overexpression of c- abl inhibits growth by causing cell cycle arrest. Growth suppression r equires tyrosine kinase activity, nuclear localization, and an intact SH2 domain. Overexpression of dominant negative c-abl disrupts cell cy cle control and enhances transformation by tyrosine kinases, G protein s, and transcription factor oncogenes. These findings suggest that c-a bl acts as a negative regulator of cell growth. This growth suppressiv e activity is functionally similar to that of tumor suppressor genes s uch as p53 and Rb.