Oncogenic activation of c-ABL by mutation within its last exon

Mol Cell Biol. 1993 Aug;13(8):4967-75. doi: 10.1128/mcb.13.8.4967-4975.1993.


The c-ABL proto-oncogene is a predominantly nuclear localized tyrosine kinase. A random mutagenesis scheme was used to isolate c-ABL mutants whose expression produced a transformed phenotype in rodent fibroblast cells. An in-frame deletion within the central region of the last exon was identified in one ABL mutant. The mechanism of c-ABL oncogenic activation by mutation within the last exon differs both functionally and structurally from those of v-ABL and BCR/ABL. This class of ABL mutants shows increased tyrosine phosphorylation of cellular proteins in vivo but low levels of autophosphorylation. Last-exon ABL mutants are distinguished from v-ABL or BCR/ABL by their inability to transform primary bone marrow cells or support the growth of transformed pre-B cells. These findings define a new mechanism of oncogenic activation for the ABL kinase through mutations in the last exon which do not require amino-terminal deletions or mutations within the src homology regions.

Publication types

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

MeSH terms

  • 3T3 Cells
  • Animals
  • Base Sequence
  • Cell Compartmentation
  • Cell Transformation, Neoplastic / genetics*
  • Cytoplasm / metabolism
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Exons
  • Genes, abl*
  • Mice
  • Molecular Sequence Data
  • Mutation
  • Oligonucleotides / chemistry
  • Protein Kinases / metabolism
  • Proto-Oncogene Proteins c-abl / genetics*
  • Recombinant Proteins
  • Sequence Deletion
  • Structure-Activity Relationship


  • DNA-Binding Proteins
  • Oligonucleotides
  • Recombinant Proteins
  • Protein Kinases
  • Proto-Oncogene Proteins c-abl