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    A specific PTPRC/CD45 phosphorylation event governed by stem cell chemokine CXCL12 regulates primitive hematopoietic cell motility.

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    Authors
    Williamson, Andrew J K
    Pierce, Andrew
    Jaworska, Ewa
    Zhou, Cong
    Aspinall-O'Dea, Mark
    Lancashire, Lee J
    Unwin, Richard D
    Abraham, S
    Walker, Michael J
    Cadeco, S
    Spooncer, Elaine
    Holyoake, T
    Whetton, Anthony D
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    Issue Date
    2013-11
    
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    Abstract
    CXCL12 governs cellular motility, a process deregulated by hematopoietic stem cell oncogenes such as p210-BCR-ABL. A phosphoproteomics approach to the analysis of a hematopoietic progenitor cell line treated with CXCL12 and the Rac 1 and 2 inhibitor NSC23766 has been employed to objectively discover novel mechanisms for regulation of stem cells in normal and malignant hematopoiesis. The proteomic data sets identified new aspects of CXCL12-mediated signaling and novel features of stem cell regulation. We also identified a novel phosphorylation event in hematopoietic progenitor cells that correlated with motile response and governed by the chemotactic factor CXCL12. The novel phosphorylation site on PTPRC/CD45; a protein tyrosine phosphatase, was validated by raising an antibody to the site and also using a mass spectrometry absolute quantification strategy. Site directed mutagenesis and inhibitor studies demonstrated that this single phosphorylation site governs hematopoietic progenitor cell and lymphoid cell motility, lies downstream from Rac proteins and potentiates Src signaling. We have also demonstrated that PTPRC/CD45 is down-regulated in leukemogenic tyrosine kinase expressing cells. The use of discovery proteomics has enabled further understanding of the regulation of PTPRC/CD45 and its important role in cellular motility in progenitor cells.
    Citation
    A specific PTPRC/CD45 phosphorylation event governed by stem cell chemokine CXCL12 regulates primitive hematopoietic cell motility. 2013, 12 (11):3319-29 Mol Cell Proteomics
    Journal
    Molecular & Cellular Proteomics
    URI
    http://hdl.handle.net/10541/314872
    DOI
    10.1074/mcp.M112.024604
    PubMed ID
    23997015
    Type
    Article
    Language
    en
    ISSN
    1535-9484
    ae974a485f413a2113503eed53cd6c53
    10.1074/mcp.M112.024604
    Scopus Count
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    All Paterson Institute for Cancer Research

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