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

Sjöblom, Tobias; Boureux, A; Rönnstrand, Lars LU ; Heldin, Carl-Henrik; Ghysdael, Jacques and Östman, Arne (1999) In Oncogene 18(50). p.7055-7062
Abstract
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... (More)
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. (Less)
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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
in
Oncogene
volume
18
issue
50
pages
7055 - 7062
publisher
Nature Publishing Group
ISSN
1476-5594
language
English
LU publication?
no
id
a9812124-61e8-464d-87c0-956006104bac (old id 1782636)
date added to LUP
2011-02-07 17:36:43
date last changed
2016-06-29 09:04:33
@article{a9812124-61e8-464d-87c0-956006104bac,
  abstract     = {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.},
  author       = {Sjöblom, Tobias and Boureux, A and Rönnstrand, Lars and Heldin, Carl-Henrik and Ghysdael, Jacques and Östman, Arne},
  issn         = {1476-5594},
  keyword      = {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},
  language     = {eng},
  number       = {50},
  pages        = {7055--7062},
  publisher    = {Nature Publishing Group},
  series       = {Oncogene},
  title        = {Characterization of the chronic myelomonocytic leukemia associated TEL-PDGF beta R fusion protein},
  volume       = {18},
  year         = {1999},
}