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Blood, 15 September 2004, Vol. 104, No. 6, pp. 1703-1710. Prepublished online as a Blood First Edition Paper on April 22, 2004; DOI 10.1182/blood-2003-10-3428. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-10-3428v1 104/6/1703    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 Chen, J. Articles by Byzova, T. V. Search for Related Content PubMed PubMed Citation Articles by Chen, J. Articles by Byzova, T. V. 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 Impaired platelet responses to thrombin and collagen in AKT-1–deficient mice Juhua Chen, Sarmishtha De, Derek S. Damron, William S. Chen, Nissim Hay, and Tatiana V. Byzova From the Department of Molecular Cardiology and Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Department of Anesthesiology, Cleveland Clinic Foundation, Cleveland, OH; and Department of Molecular Genetics, College of Medicine, University of Illinois at Chicago. We investigated the role of Akt-1, one of the major downstream effectors of phosphoinositide 3-kinase (PI3K), in platelet function using mice in which the gene for Akt-1 had been inactivated. Using ex vivo techniques, we showed that Akt-1-deficient mice exhibited impaired platelet aggregation and spreading in response to various agonists. These differences were most apparent in platelets activated with low concentrations of thrombin. Although Akt-1 is not the predominant Akt isoform in mouse platelets, its absence diminished the amount of total phospho-Akt and inhibited increases in intracellular Ca2+ concentration in response to thrombin. Moreover, thrombin-induced platelet -granule release as well as release of adenosine triphosphate from dense granules was also defective in Akt-1-null platelets. Although the absence of Akt-1 did not influence expression of the major platelet receptors for thrombin and collagen, fibrinogen binding in response to these agonists was significantly reduced. As a consequence of impaired IIb3 activation and platelet aggregation, Akt-1 null mice showed significantly longer bleeding times than wild-type mice. 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