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Blood, 1 June 2005, Vol. 105, No. 11, pp. 4369-4376. Prepublished online as a Blood First Edition Paper on February 8, 2005; DOI 10.1182/blood-2004-10-4098. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-10-4098v1 105/11/4369    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 Hughan, S. C. Articles by Watson, S. P. Search for Related Content PubMed PubMed Citation Articles by Hughan, S. C. Articles by Watson, S. P. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Selective impairment of platelet activation to collagen in the absence of GATA1 Sascha C. Hughan, Yotis Senis, Denise Best, Angela Thomas, Jon Frampton, Paresh Vyas, and Steve P. Watson From the Centre for Cardiovascular Sciences, Institute of Biomedical Research, University of Birmingham, Birmingham, United Kingdom; the Department of Pharmacology, University of Oxford, Oxford, United Kingdom; the Department of Paediatric Haematology at the Royal Sick Children's Hospital, Edinburgh, Scotland; the Department of Anatomy, Institute of Biomedical Research, Division of Infection and Immunity, The Medical School, University of Birmingham, Birmingham, United Kingdom; and the Department of Haematology and MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford, United Kingdom. Defects in the X-linked DNA-binding megakaryocyte transcription factor GATA1 cause thrombocytopenia and abnormal platelet function. However, detailed studies of GATA1 function in platelet activation are lacking. Here, we studied platelets from GATA1-deficient mice and from a male patient (S14) with a bleeding diathesis attributed to a single amino acid substitution (R216Q) in the N-terminal GATA1 zinc finger that alters binding to DNA. In both cases there was inhibition of aggregation to collagen and decreased tyrosine phosphorylation of glycoprotein VI (GPVI)–signaling proteins. This effect was more marked in GATA1-deficient murine platelets, where it was associated with a significant reduction in surface GPVI expression. Moreover, both human and murine GATA1-mutant platelets showed reduced adhesion and aggregate formation on a collagen matrix at an intermediate rate of shear, although this could not be accounted solely by the thrombocytopenia and altered GPVI expression, indicating that GATA1 regulates additional factors important for platelet activation under shear. In contrast, there was no inhibition of responses to G protein–coupled receptor agonists in GATA1-perturbed platelets. Our results are consistent with GATA1 regulating some but not all pathways of platelet activation, leading to an impairment of aggregate formation under flow, which cannot be attributed solely to the thrombocytopenia. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. L. Balduini, E. De Candia, and A. Savoia Why the disorder induced by GATA1 Arg216Gln mutation should be called "X-linked thrombocytopenia with thalassemia" rather than "X-linked gray platelet syndrome" Blood, October 1, 2007; 110(7): 2770 - 2771. [Full Text] [PDF] V. N. Tubman, J. E. Levine, D. R. Campagna, R. Monahan-Earley, A. M. Dvorak, E. J. Neufeld, and M. D. Fleming X-linked gray platelet syndrome due to a GATA1 Arg216Gln mutation Blood, April 15, 2007; 109(8): 3297 - 3299. [Abstract] [Full Text] [PDF]

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