NDLI: A Specific PTPRC/CD45 Phosphorylation Event Governed by Stem Cell Chemokine CXCL12 Regulates Primitive Hematopoietic Cell Motility

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Williamson, Andrew J. K. Pierce, Andrew Jaworska, Ewa Zhou, Cong Aspinall-O'Dea, Mark Lancashire, Lee Unwin, Richard D. Abraham, Sheela A. Walker, Michael J. Cadecco, Sara Spooncer, Elaine Holyoake, Tessa L. Whetton, Anthony D.
Description	Author Affiliation: Williamson AJ ( Stem Cell and Leukaemia Proteomics Laboratory, School of Cancer and Enabling Sciences, Manchester Academic Health Science Centre, University of Manchester, 27 Palatine Rd, Manchester, M20 4QL)
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.
File Format	HTM / HTML
ISSN	15359476
e-ISSN	15359484
DOI	10.1074/mcp.M112.024604
Journal	Molecular & Cellular Proteomics
Issue Number	11
Volume Number	12
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2013-11-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Proteomics Antigens, Cd45 Metabolism Cell Movement Physiology Chemokine Cxcl12 Hematopoietic Stem Cells Aminoquinolines Pharmacology Animals Chemistry Genetics Cell Line Drug Effects Enzyme Inhibitors Fusion Proteins, Bcr-abl Leukemia, Myelogenous, Chronic, Bcr-abl Positive Pathology Mice Mice, Inbred C57bl Mice, Knockout Phosphorylation Proteomics Pyrimidines Signal Transduction Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Medicine Analytical Chemistry Molecular Biology Biochemistry

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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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A Specific PTPRC/CD45 Phosphorylation Event Governed by Stem Cell Chemokine CXCL12 Regulates Primitive Hematopoietic Cell Motility

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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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A Specific PTPRC/CD45 Phosphorylation Event Governed by Stem Cell Chemokine CXCL12 Regulates Primitive Hematopoietic Cell Motility