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Blood, 15 June 2006, Vol. 107, No. 12, pp. 4888-4897. Prepublished online as a Blood First Edition Paper on February 23, 2006; DOI 10.1182/blood-2005-08-3399. This Article Full Text Full Text (PDF) Supplemental Tables All Versions of this Article: 2005-08-3399v1 107/12/4888    most recent 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 Goss, V. L. Articles by Polakiewicz, R. D. Search for Related Content PubMed PubMed Citation Articles by Goss, V. L. Articles by Polakiewicz, R. D. Related Collections Neoplasia Oncogenes and Tumor Suppressors Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA A common phosphotyrosine signature for the Bcr-Abl kinase Valerie L. Goss, Kimberly A. Lee, Albrecht Moritz, Julie Nardone, Erik J. Spek, Joan MacNeill, John Rush, Michael J. Comb, and Roberto D. Polakiewicz From Cell Signaling Technology, Danvers, MA. The Bcr-Abl fusion kinase drives oncogenesis in chronic myeloid leukemia (CML). CML patients are currently treated with the Abl tyrosine kinase inhibitor imatinib, which is effective in early stages of the disease. However, resistance to imatinib arises in later disease stages primarily because of a Bcr-Abl mutation. To gain deeper insight into Bcr-Abl signaling pathways, we generated phosphotyrosine profiles for 6 cell lines that represent 3 Bcr-Abl fusion types by using immunoaffinity purification of tyrosine phosphopeptides followed by tandem mass spectrometry. We identified 188 nonredundant tyrosine-phosphorylated sites, 77 of which are novel. By comparing the profiles, we found a number of phosphotyrosine sites common to the 6 cell lines regardless of cellular background and fusion type, several of which are decreased by imatinib treatment. Comparison of this Bcr-Abl signature with the profile of cells expressing an alternative imatinib-sensitive fusion kinase, FIP1L1-PDGFR, revealed that these kinases signal through different pathways. This phosphoproteomic study of the Bcr-Abl fusion kinase highlights novel disease markers and potential drug-responsive biomarkers and adds novel insight into the oncogenic signals driven by the Bcr-Abl kinase. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. E. Boccalatte, C. Voena, C. Riganti, A. Bosia, L. D'Amico, L. Riera, M. Cheng, B. Ruggeri, O. N. Jensen, V. L. Goss, et al. The enzymatic activity of 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase is enhanced by NPM-ALK: new insights in ALK-mediated pathogenesis and the treatment of ALCL Blood, March 19, 2009; 113(12): 2776 - 2790. [Abstract] [Full Text] [PDF] A. Ritz, G. Shakhnarovich, A. R. Salomon, and B. J. Raphael Discovery of phosphorylation motif mixtures in phosphoproteomics data Bioinformatics, January 1, 2009; 25(1): 14 - 21. [Abstract] [Full Text] [PDF] L. Cao, K. Yu, C. Banh, V. Nguyen, A. Ritz, B. J. Raphael, Y. Kawakami, T. Kawakami, and A. R. Salomon Quantitative Time-Resolved Phosphoproteomic Analysis of Mast Cell Signaling J. Immunol., November 1, 2007; 179(9): 5864 - 5876. [Abstract] [Full Text] [PDF]

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