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Blood, 1 April 2008, Vol. 111, No. 7, pp. 3522-3530. Prepublished online as a Blood First Edition Paper on February 1, 2008January 24, 2008; DOI 10.1182/blood-2007-09-111518. This Article Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2007-09-111518v1 blood-2007-09-111518v2 111/7/3522    most recent Alert me when this article is cited Alert me if a correction is posted 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 Li, D. Articles by Woulfe, D. S Search for Related Content PubMed PubMed Citation Articles by Li, D. Articles by Woulfe, D. S Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted September 7, 2007 Accepted January 15, 2008 GSK3 is a negative regulator of platelet function and thrombosis Dongjun Li, Shelley August, and Donna S Woulfe* Center for Translational Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, PA, United States * Corresponding author; email: donna.woulfe{at}jefferson.edu. Glycogen synthase kinase (GSK)3 is a ser-thr kinase that is phosphorylated by the kinase Akt. Although Akt has been shown to regulate platelet function and arterial thrombosis, its effectors in platelets remain unknown. We show here that agonist-dependent phosphorylation of GSK3 in platelets is Akt-dependent. To determine whether GSK3 regulates platelet function, platelets from mice lacking a single allele of GSK3 were compared to those of WT controls. GSK3+/- platelets demonstrated enhanced agonist-dependent aggregation, dense granule secretion, and fibrinogen binding compared to WT platelets. Treatment of human platelets with GSK3 inhibitors renders them more sensitive to agonist-induced aggregation, suggesting that GSK3 suppresses platelet function in vitro. Finally, the effect of GSK3 on platelet function in vivo was evaluated using two thrombosis models in mice. In the first, 80% of GSK3+/- mice (n=10) formed stable occlusive thrombi after ferric chloride carotid artery injury, whereas the majority of wildtype mice (67%) formed no thrombi (n=15). In a disseminated thrombosis model, deletion of a single allele of GSK3 in mice conferred enhanced sensitivity to thrombotic insult. Taken together, these results suggest that GSK3 acts as a negative regulator of platelet function in vitro and in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. M. Steele, M. T. Harper, I. C. Macaulay, C. N. Morrell, A. Perez-Tamayo, M. Foy, R. Habas, A. W. Poole, D. J. Fitzgerald, and P. B. Maguire Canonical Wnt signaling negatively regulates platelet function PNAS, November 24, 2009; 106(47): 19836 - 19841. [Abstract] [Full Text] [PDF] S. S. Smyth, D. S. Woulfe, J. I. Weitz, C. Gachet, P. B. Conley, S. G. Goodman, M. T. Roe, A. Kuliopulos, D. J. Moliterno, P. A. French, et al. G-Protein-Coupled Receptors as Signaling Targets for Antiplatelet Therapy Arterioscler Thromb Vasc Biol, April 1, 2009; 29(4): 449 - 457. [Abstract] [Full Text] [PDF]

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