期刊
BLOOD
卷 104, 期 6, 页码 1703-1710出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2003-10-3428
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- NHLBI NIH HHS [HL071625, R01 HL071625] Funding Source: Medline
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 Ca(2+) concentration in response to thrombin. Moreover, thrombin-induced platelet alpha-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 alpha(IIb)beta(3) activation and platelet aggregation, Akt-1 null mice showed significantly longer bleeding times than wild-type mice. (C) 2004 by The American Society of Hematology.
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