The TEL/platelet-derived growth factor β receptor (PDGFβR) fusion in chronic myelomonocytic leukemia is a transforming protein that self-associates and activates PDGFβR kinase-dependent signaling pathways
作者： M. Carroll , M. H. Tomasson , G. F. Barker , T. R. Golub , D. G. Gilliland
关键词: Tyrosine 、 Phosphorylation 、 Signal transduction 、 Platelet-derived growth factor receptor 、 Receptor tyrosine kinase 、 Tyrosine kinase 、 Molecular biology 、 Fusion protein 、 Biology 、 Kinase activity
摘要: The TEL/PDGF beta R fusion protein is the product of t(5;12) translocation in patients with chronic myelomonocytic leukemia. an unusual a putative transcription factor, TEL, to receptor tyrosine kinase. fuses amino terminus containing helix-loop-helix (HLH) domain, transmembrane and cytoplasmic domain PDGF R. We hypothesized that self-association, mediated by HLH would lead constitutive activation kinase cellular transformation. Analysis vitro-translated TEL/ confirmed self-associated self-association was abrogated deletion 51 aa within TEL domain. In vivo, detected as 100-kDa constitutively phosphorylated on transformed murine hematopoietic cell line Ba/F3 interleukin 3 growth factor independence. Transformation cells required activity portion protein. Immunoblotting demonstrated associated multiple signaling molecules known associate activated R, including phospholipase C gamma 1, SHP2, phosphoinositol-3-kinase. novel transforming self-associates activates R-dependent pathways. Oligomerization dependent provides further evidence highly conserved among ETS family members, motif.
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