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- Title
Characterization of the chronic myelomonocytic leukemia associated TEL-PDGFβR fusion protein.
- Authors
Sjöblom, Tobias; Boureux, Anthony; Rönnstrand, Lars; Heldin, Carl-Henrik; Ghysdael, Jacques; Östman, Arne
- Abstract
The t(5;12) translocation, associated with chronic myelomonocytic leukemia, generates a novel gene encoding a protein, TEL-PDGFβR, composed of the 154 amino-terminal amino acids of the transcription factor TEL and the transmembrane and intracellular part of the PDGF β-receptor (PDGFβR). 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-PDGFβR and also indicated that the TEL moiety activates the tyrosine kinase of the PDGFβR through the formation of TEL-PDGFβR oligomers. We demonstrate that tyrosine phosphorylation of the fusion protein can be attenuated through overexpression of the TEL part of TEL-PDGFβR, suggesting a strategy for antagonizing the signaling of TEL-PDGFβR, and other TEL-fusion proteins containing tyrosine kinase domains. Comparison of BaF/3 cell lines expressing TEL-PDGFβR and ligand-stimulated PDGFβR revealed that only TEL-PDGFβR expression conferred IL-3-independent growth, suggesting differences in signaling capacity of the two proteins. Finally, tyrosine residues 17 and 27 in TEL-PDGFβR was identified as autophosphorylation sites in TEL-PDGFβR.
- Subjects
LEUKEMIA; PROTEINS; GROWTH factors
- Publication
Oncogene, 1999, Vol 18, Issue 50, p7055
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1203190