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

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.

Pubmed ID: 1712671

Authors

  • Pendergast AM
  • Muller AJ
  • Havlik MH
  • Maru Y
  • Witte ON

Journal

Cell

Publication Data

July 12, 1991

Associated Grants

None

Mesh Terms

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