Characterization of the chronic myelomonocytic leukemia associated TEL-PDGF beta R fusion protein
(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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- author
- Sjöblom, Tobias ; Boureux, A ; Rönnstrand, Lars LU ; Heldin, Carl-Henrik ; Ghysdael, Jacques and Östman, Arne
- publishing date
- 1999
- type
- Contribution to journal
- publication status
- published
- subject
- 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
- in
- Oncogene
- volume
- 18
- issue
- 50
- pages
- 7055 - 7062
- publisher
- Nature Publishing Group
- ISSN
- 1476-5594
- language
- English
- LU publication?
- no
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Experimental Clinical Chemistry (013016010)
- id
- a9812124-61e8-464d-87c0-956006104bac (old id 1782636)
- date added to LUP
- 2016-04-04 08:52:56
- date last changed
- 2019-05-22 02:18:10
@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}}, 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}}, 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}}, }