BCR sequences essential for transformation by the BCR-ABL oncogene bind to the ABL SH2 regulatory domain in a non-phosphotyrosine-dependent manner

Cell. 1991 Jul 12;66(1):161-71. doi: 10.1016/0092-8674(91)90148-r.

Abstract

BCR-ABL is a chimeric oncogene implicated in the pathogenesis of Philadelphia chromosome-positive human leukemias. BCR first exon sequences specifically activate the tyrosine kinase and transforming potential of BCR-ABL. We have tested the hypothesis that activation of BCR-ABL may involve direct interaction between BCR sequences and the tyrosine kinase regulatory domains of ABL. Full-length c-BCR as well as BCR sequences retained in BCR-ABL bind specifically to the SH2 domain of ABL. The binding domain has been localized within the first exon of BCR and consists of at least two SH2-binding sites. This domain is essential for BCR-ABL-mediated transformation. Phosphoserine/phosphothreonine but not phosphotyrosine residues on BCR are required for interaction with the ABL SH2 domain. These findings extend the range of potential SH2-protein interactions in growth control pathways and suggest a function for SH2 domains in the activation of the BCR-ABL oncogene as well as a role for BCR in cellular signaling pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cell Line
  • Cell Transformation, Neoplastic*
  • Exons
  • Fusion Proteins, bcr-abl / genetics*
  • Genes, abl*
  • Genetic Variation
  • Humans
  • Insecta
  • Molecular Sequence Data
  • Oncogene Proteins / genetics*
  • Oncogenes*
  • Phosphotyrosine
  • Plasmids
  • Protein Biosynthesis
  • Protein-Tyrosine Kinases*
  • Proto-Oncogene Proteins c-bcr
  • Proto-Oncogene Proteins*
  • Regulatory Sequences, Nucleic Acid
  • Transcription, Genetic
  • Transfection
  • Tyrosine / analogs & derivatives

Substances

  • Oncogene Proteins
  • Proto-Oncogene Proteins
  • Phosphotyrosine
  • Tyrosine
  • Protein-Tyrosine Kinases
  • Fusion Proteins, bcr-abl
  • BCR protein, human
  • Proto-Oncogene Proteins c-bcr