The nuclear tyrosine kinase c-Abl negatively regulates cell growth

Cell. 1994 Apr 8;77(1):121-31. doi: 10.1016/0092-8674(94)90240-2.


c-Abl is a tyrosine kinase localized primarily in the nucleus. Previous assays for abl function rely on cellular transformation by abl mutants, 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 requires tyrosine kinase activity, nuclear localization, and an intact SH2 domain. Overexpression of dominant negative c-abl disrupts cell cycle control and enhances transformation by tyrosine kinases, G proteins, and transcription factor oncogenes. These findings suggest that c-abl acts as a negative regulator of cell growth. This growth suppressive activity is functionally similar to that of tumor suppressor genes such as p53 and Rb.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Animals
  • Cell Cycle*
  • Cell Nucleus / enzymology*
  • Cell Transformation, Neoplastic
  • Gene Expression
  • Genes, Dominant
  • Genes, abl*
  • Growth Inhibitors
  • Mice
  • Oncogenes
  • Phosphotyrosine
  • Protein-Tyrosine Kinases / physiology*
  • Proto-Oncogene Proteins c-abl / genetics*
  • Transfection
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism


  • Growth Inhibitors
  • Phosphotyrosine
  • Tyrosine
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-abl