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Characterization of the chronic myelomonocytic leukemia associated TEL-PDGF beta R fusion protein

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Author

  • Tobias Sjöblom
  • A Boureux
  • Lars Rönnstrand
  • Carl-Henrik Heldin
  • Jacques Ghysdael
  • Arne Östman

Summary, in English

The t(5;12) translocation, associated with chronic myelomonocytic leukemia, generates a novel gene encoding a protein, TEL-PDGF beta R, composed of the 154 amino-terminal amino acids of the transcription factor TEL and the transmembrane and intracellular part of the PDGF beta-receptor (PDGF beta R). TEL also occurs as a tumor-associated fusion partner for the tyrosine kinases c-ABL, JAK2 and TRK-C. Previous studies have demonstrated growth promoting activity of TEL-PDGF beta R and also indicated that the TEL moiety activates the tyrosine kinase of the PDGF beta R through the formation of TEL-PDGF beta R oligomers. We demonstrate that tyrosine phosphorylation of the fusion protein can be attenuated through overexpression of the TEL part of TEL-PDGF beta R, suggesting a strategy for antagonizing the signaling of TEL-PDGF beta R, and other TEL-fusion proteins containing tyrosine kinase domains. Comparison of BaF/3 cell lines expressing TEL-PDGF beta R and ligand-stimulated PDGF beta R revealed that only TEL-PDGF beta R expression conferred IL-3-independent growth, suggesting differences in signaling capacity of the two proteins. Finally, tyrosine residues 17 and 27 in TEL-PDGF beta R was identified as autophosphorylation sites in TEL-PDGF beta R.

Publishing year

1999

Language

English

Pages

7055-7062

Publication/Series

Oncogene

Volume

18

Issue

50

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Medicinal Chemistry

Keywords

  • Animals Base Sequence COS Cells DNA Primers Humans Leukemia
  • Myelomonocytic
  • Chronic/*genetics Ligands Mutagenesis
  • Fusion/*genetics/metabolism Phenylalanine/genetics Phosphorylation Tumor Cells
  • Site-Directed Oncogene Proteins
  • Cultured Tyrosine/genetics/metabolism

Status

Published

ISBN/ISSN/Other

  • ISSN: 1476-5594