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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sternberg, D. W. Articles by Gilliland, D. G. Search for Related Content PubMed PubMed Citation Articles by Sternberg, D. W. Articles by Gilliland, D. G. Related Collections Signal Transduction Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 December 2001, Vol. 98, No. 12, pp. 3390-3397 NEOPLASIA The TEL/PDGFR fusion in chronic myelomonocytic leukemia signals through STAT5-dependent and STAT5-independent pathways David W. Sternberg, Michael H. Tomasson, Martin Carroll, David P. Curley, George Barker, Michael Caprio, Alyson Wilbanks, Andrius Kazlauskas, and D. Gary Gilliland From the Howard Hughes Medical Institute, Harvard Medical School, Schepens Eye Research Institute, and Brigham and Women's Hospital, Boston, MA. The TEL/PDGFR gene, which encodes a fusion protein containing the ETS-family member TEL fused to the protein-tyrosine kinase domain of the platelet-derived growth factor receptor- (PDGFR), confers interleukin 3 (IL-3)-independent growth on Ba/F3 hematopoietic cells. TEL/PDGFR mutants have been generated that contain tyrosine-to-phenylalanine (TyrPhe) substitutions at phosphorylation sites present in the native PDGFR to assess the role of these sites in cell transformation by TEL/PDGFR. Similar to previous findings in a murine bone marrow transplantation model, full transformation of Ba/F3 cells to IL-3-independent survival and proliferation required the TEL/PDGFR juxtamembrane and carboxy terminal phosphorylation sites. In contrast to previous reports concerning comparable mutants in the native PDGFR, each of the TEL/PDGFR mutants is fully active as a protein-tyrosine kinase. Expression of the TEL/PDGFR fusion protein causes hyperphosphorylation and activation of signal transducer and activator of transcription (STAT5), and this activation of STAT5 requires the juxtamembrane Tyr579 and Tyr581 in the TEL/PDGFR fusion. Hyperphosphosphorylation of phospholipase C (PLC) and the p85 subunit of phosphatidylinositol 3-kinase (PI3K) requires the carboxy terminal tyrosine residues of TEL/PDGFR. Thus, full transformation of Ba/F3 cells by TEL/PDGFR requires engagement of PI3K and PLC and activation of STAT5. Taken together with the growth properties of cells transformed by the TEL/PDGFR variants, these findings indicate that a minimal combination of these signaling intermediates contributes to hematopoietic transformation by the wild-type TEL/PDGFR fusion. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. V. Barry, J. J. Clark, J. Cools, J. Roesel, and D. G. Gilliland Uniform sensitivity of FLT3 activation loop mutants to the tyrosine kinase inhibitor midostaurin Blood, December 15, 2007; 110(13): 4476 - 4479. [Abstract] [Full Text] [PDF] J. A. Cain, Z. Xiang, J. O'Neal, F. Kreisel, A. Colson, H. Luo, L. Hennighausen, and M. H. Tomasson Myeloproliferative disease induced by TEL-PDGFRB displays dynamic range sensitivity to Stat5 gene dosage Blood, May 1, 2007; 109(9): 3906 - 3914. [Abstract] [Full Text] [PDF] J. L. Rocnik, R. Okabe, J.-C. Yu, B. H. Lee, N. 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