A specific PTPRC/CD45 phosphorylation event governed by stem cell chemokine CXCL12 regulates primitive hematopoietic cell motility.
Authors
Williamson, Andrew J KPierce, 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
Issue Date
2013-11
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Show full item recordAbstract
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 ProteomicsJournal
Molecular & Cellular ProteomicsDOI
10.1074/mcp.M112.024604PubMed ID
23997015Type
ArticleLanguage
enISSN
1535-9484ae974a485f413a2113503eed53cd6c53
10.1074/mcp.M112.024604
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