Proceedings of the National Academy of Sciences - PNAS, 1996-12, Vol.93 (25), p.14845-14850
1996
Details
- Autor(en) / Beteiligte
- Titel
- The TEL/Platelet-Derived Growth Factor β Receptor (PDGFβ R) Fusion in Chronic Myelomonocytic Leukemia is a Transforming Protein that Self-Associates and Activates PDGFβ R Kinase-Dependent Signaling Pathways
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 1996-12, Vol.93 (25), p.14845-14850
- Ort / Verlag
- United States: National Academy of Sciences of the United States of America
- Erscheinungsjahr
- 1996
- Link zum Volltext
- Quelle
- EZB-FREE-00999 freely available EZB journals
- Beschreibungen/Notizen
- The TEL/PDGFβ R fusion protein is the product of the t (5;12) translocation in patients with chronic myelomonocytic leukemia. The TEL/PDGFβ R is an unusual fusion of a putative transcription factor, TEL, to a receptor tyrosine kinase. The translocation fuses the amino terminus of TEL, containing the helix-loop-helix (HLH) domain, to the transmembrane and cytoplasmic domain of the PDGFβ R. We hypothesized that TEL/PDGFβ R self-association, mediated by the HLH domain of TEL, would lead to constitutive activation of the PDGFβ R tyrosine kinase domain and cellular transformation. Analysis of in vitro-translated TEL/TEL/PDGFβ R confirmed that the protein self-associated and that self-association was abrogated by deletion of 51 aa within the TEL HLH domain. In vivo TEL/PDGFβ R was detected as a 100-kDa protein that was constitutively phosphorylated on tyrosine and transformed the murine hematopoietic cell line Ba/F3 to interleukin 3 growth factor independence. Transformation of Ba/F3 cells required the HLH domain of TEL and the kinase activity of the PDGFβ R portion of the fusion protein. Immunoblotting demonstrated that TEL/PDGFβ R associated with multiple signaling molecules known to associate with the activated PDGFβ R, including phospholipase C γ 1, SHP2, and phosphoinositol-3-kinase. TEL/PDGFβ R is a novel transforming protein that self-associates and activates PDGFβ R-dependent signaling pathways. Oligomerization of TEL/PDGFβ R that is dependent on the TEL HLH domain provides further evidence that the HLH domain, highly conserved among ETS family members, is a self-association motif.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.93.25.14845Titel-ID: cdi_pnas_primary_93_25_14845_fulltext
- Format
- –
- Schlagworte
- 3T3 cells, Antibodies, Biological Sciences, Cell growth, Cell lines, Dimerization, DNA, DNA-Binding Proteins - genetics, DNA-Binding Proteins - metabolism, ETS Translocation Variant 6 Protein, Humans, Leukemia, Myelomonocytic, Chronic - genetics, Leukemia, Myelomonocytic, Chronic - metabolism, Molecular Sequence Data, Molecules, Myeloid cells, Neoplasm Proteins - genetics, Neoplasm Proteins - metabolism, NIH 3T3 cells, Protein-Tyrosine Kinases - metabolism, Proto-Oncogene Proteins c-ets, Receptor, Platelet-Derived Growth Factor beta, Receptors, Platelet-Derived Growth Factor - metabolism, Repressor Proteins, Signal Transduction, Transcription Factors - genetics, Transcription Factors - metabolism, Transformed cell line, Translocation, Genetic