PMID- 10597306 OWN - NLM STAT- MEDLINE DCOM- 20000104 LR - 20131121 IS - 0950-9232 (Print) IS - 0950-9232 (Linking) VI - 18 IP - 50 DP - 1999 Nov 25 TI - Characterization of the chronic myelomonocytic leukemia associated TEL-PDGF beta R fusion protein. PG - 7055-62 AB - 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. FAU - Sjoblom, T AU - Sjoblom T AD - Ludwig Institute for Cancer Research, Uppsala, Sweden. FAU - Boureux, A AU - Boureux A FAU - Ronnstrand, L AU - Ronnstrand L FAU - Heldin, C H AU - Heldin CH FAU - Ghysdael, J AU - Ghysdael J FAU - Ostman, A AU - Ostman A LA - eng PT - Journal Article PL - England TA - Oncogene JT - Oncogene JID - 8711562 RN - 0 (DNA Primers) RN - 0 (Ligands) RN - 0 (Oncogene Proteins, Fusion) RN - 0 (TEL-PDGFRbeta fusion protein, human) RN - 42HK56048U (Tyrosine) RN - 47E5O17Y3R (Phenylalanine) SB - IM MH - Animals MH - Base Sequence MH - COS Cells MH - DNA Primers MH - Humans MH - Leukemia, Myelomonocytic, Chronic/*genetics MH - Ligands MH - Mutagenesis, Site-Directed MH - Oncogene Proteins, Fusion/*genetics/metabolism MH - Phenylalanine/genetics MH - Phosphorylation MH - Tumor Cells, Cultured MH - Tyrosine/genetics/metabolism EDAT- 1999/12/22 00:00 MHDA- 1999/12/22 00:01 CRDT- 1999/12/22 00:00 PHST- 1999/12/22 00:00 [pubmed] PHST- 1999/12/22 00:01 [medline] PHST- 1999/12/22 00:00 [entrez] AID - 10.1038/sj.onc.1203190 [doi] PST - ppublish SO - Oncogene. 1999 Nov 25;18(50):7055-62. doi: 10.1038/sj.onc.1203190.