Activation of the c-Abl tyrosine kinase in the stress response to DNA-damaging agents

Nature. 1995 Aug 31;376(6543):785-8. doi: 10.1038/376785a0.


The product of the c-abl gene is a non-receptor tyrosine kinase that is localized to the nucleus and cytoplasm. The precise function of c-Abl is unknown. Here we show that ionizing radiation activates c-Abl. Similar results were obtained with the alkylating agents cis-platinum and mitomycin C. We also demonstrate that cells deficient in c-Abl fail to activate Jun kinase (JNK/SAP kinase) after ionizing radiation or alkylating agent exposure and that reconstitution of c-Abl in these cells restores that response. In contrast, the stress response to tumour-necrosis factor is stimulated by a c-Abl-independent mechanism. These findings indicate that c-abl is involved in the stress response to DNA-damaging agents.

Publication types

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

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cisplatin / pharmacology
  • DNA / drug effects*
  • DNA / metabolism
  • DNA Damage*
  • Enzyme Activation
  • Humans
  • JNK Mitogen-Activated Protein Kinases*
  • MAP Kinase Kinase 4
  • Mice
  • Mitogen-Activated Protein Kinase Kinases*
  • Mitomycins / pharmacology
  • Molecular Sequence Data
  • Peptides / metabolism
  • Protein Kinases / metabolism
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Protein-Tyrosine Kinases / radiation effects
  • Proto-Oncogene Proteins c-abl / genetics
  • Proto-Oncogene Proteins c-abl / metabolism*
  • Proto-Oncogene Proteins c-abl / radiation effects
  • Proto-Oncogene Proteins c-jun / metabolism
  • Radiation, Ionizing


  • Mitomycins
  • Peptides
  • Proto-Oncogene Proteins c-jun
  • DNA
  • Protein Kinases
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-abl
  • JNK Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases
  • Cisplatin