Characterization of the chronic myelomonocytic leukemia associated TEL-PDGF beta R fusion protein
Författare
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.
Publiceringsår
1999
Språk
Engelska
Sidor
7055-7062
Publikation/Tidskrift/Serie
Oncogene
Volym
18
Issue
50
Dokumenttyp
Artikel i tidskrift
Förlag
Nature Publishing Group
Ämne
- Medicinal Chemistry
Nyckelord
- 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/Övrigt
- ISSN: 1476-5594