Differential complementation of Bcr-Abl point mutants with c-Myc

Science. 1994 Apr 15;264(5157):424-6. doi: 10.1126/science.8153630.


A complementation strategy was developed to define the signaling pathways activated by the Bcr-Abl tyrosine kinase. Transformation inactive point mutants of Bcr-Abl were tested for complementation with c-Myc. Single point mutations in the Src-homology 2 (SH2) domain, the major tyrosine autophosphorylation site of the kinase domain, and the Grb-2 binding site in the Bcr region impaired the transformation of fibroblasts by Bcr-Abl. Hyperexpression of c-Myc efficiently restored transformation activity only to the Bcr-Abl SH2 mutant. These data support a model in which Bcr-Abl activates at least two independent pathways for transformation. This strategy may be useful for discerning signaling pathways activated by other oncogenes.

Publication types

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

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Line
  • Cell Transformation, Neoplastic*
  • Fusion Proteins, bcr-abl / genetics*
  • Fusion Proteins, bcr-abl / physiology
  • GRB2 Adaptor Protein
  • Gene Expression
  • Genes, abl*
  • Genes, myc*
  • Genetic Complementation Test
  • Molecular Sequence Data
  • Phosphorylation
  • Point Mutation
  • Proteins / metabolism
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / physiology
  • Rats
  • Retroviridae / physiology
  • Signal Transduction
  • Transfection
  • Tyrosine / metabolism


  • Adaptor Proteins, Signal Transducing
  • GRB2 Adaptor Protein
  • Grb2 protein, rat
  • Proteins
  • Proto-Oncogene Proteins c-myc
  • Tyrosine
  • Fusion Proteins, bcr-abl