SEARCH:   Advanced

Blood, 1 April 2008, Vol. 111, No. 7, pp. 3522-3530. Prepublished online as a Blood First Edition Paper on February 1, 2008; DOI 10.1182/blood-2007-09-111518. This Article Full Text 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 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 Li, D. Articles by Woulfe, D. S. Search for Related Content PubMed PubMed Citation Articles by Li, D. Articles by Woulfe, D. S. Related Collections Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY GSK3β is a negative regulator of platelet function and thrombosis Dongjun Li1, Shelley August1, and Donna S. Woulfe1 1 Center for Translational Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, PA Glycogen synthase kinase (GSK)3β 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 GSK3β in platelets is Akt dependent. To determine whether GSK3β regulates platelet function, platelets from mice lacking a single allele of GSK3β were compared with those of wild-type (WT) controls. GSK3β+/– platelets demonstrated enhanced agonist-dependent aggregation, dense granule secretion, and fibrinogen binding, compared with 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 GSK3β on platelet function in vivo was evaluated using 2 thrombosis models in mice. In the first, 80% of GSK3β+/– mice (n = 10) formed stable occlusive thrombi after ferric chloride carotid artery injury, whereas the majority of wild-type mice (67%) formed no thrombi (n = 15). In a disseminated thrombosis model, deletion of a single allele of GSK3β in mice conferred enhanced sensitivity to thrombotic insult. Taken together, these results suggest that GSK3β 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: 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]

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020