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    Eight-channel iTRAQ enables comparison of the activity of six leukemogenic tyrosine kinases.

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    Authors
    Pierce, Andrew
    Unwin, Richard D
    Evans, Caroline A
    Griffiths, Stephen D
    Carney, Louise
    Zhang, Liqun
    Jaworska, Ewa
    Lee, Chia-Fang
    Blinco, David
    Okoniewski, Michal J
    Miller, Crispin J
    Bitton, Danny A
    Spooncer, Elaine
    Whetton, Anthony D
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    Affiliation
    Stem Cell and Leukaemia Proteomics Laboratory, University of Manchester, Christie Hospital, Kinnaird House, Kinnaird Road, Manchester M204QL, United Kingdom.
    Issue Date
    2008-05
    
    Metadata
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    Abstract
    There are a number of leukemogenic protein-tyrosine kinases (PTKs) associated with leukemic transformation. Although each is linked with a specific disease their functional activity poses the question whether they have a degree of commonality in their effects upon target cells. Exon array analysis of the effects of six leukemogenic PTKs (BCR/ABL, TEL/PDGFRbeta, FIP1/PDGFRalpha, D816V KIT, NPM/ALK, and FLT3ITD) revealed few common effects on the transcriptome. It is apparent, however, that proteome changes are not directly governed by transcriptome changes. Therefore, we assessed and used a new generation of iTRAQ tagging, enabling eight-channel relative quantification discovery proteomics, to analyze the effects of these six leukemogenic PTKs. Again these were found to have disparate effects on the proteome with few common targets. BCR/ABL had the greatest effect on the proteome and had more effects in common with FIP1/PDGFRalpha. The proteomic effects of the four type III receptor kinases were relatively remotely related. The only protein commonly affected was eosinophil-associated ribonuclease 7. Five of six PTKs affected the motility-related proteins CAPG and vimentin, although this did not correspond to changes in motility. However, correlation of the proteomics data with that from the exon microarray not only showed poor levels of correlation between transcript and protein levels but also revealed alternative patterns of regulation of the CAPG protein by different oncogenes, illustrating the utility of such a combined approach.
    Citation
    Eight-channel iTRAQ enables comparison of the activity of six leukemogenic tyrosine kinases. 2008, 7 (5):853-63 Mol. Cell Proteomics
    Journal
    Molecular & Cellular Proteomics
    URI
    http://hdl.handle.net/10541/55053
    DOI
    10.1074/mcp.M700251-MCP200
    PubMed ID
    17951628
    Type
    Article
    Language
    en
    ISSN
    1535-9484
    ae974a485f413a2113503eed53cd6c53
    10.1074/mcp.M700251-MCP200
    Scopus Count
    Collections
    Applied Computational Biology and Bioinformatics
    All Paterson Institute for Cancer Research
    School of Cancer and Imaging Sciences

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