| First Author | Chen J | Year | 2004 |
| Journal | Blood | Volume | 104 |
| Issue | 6 | Pages | 1703-10 |
| PubMed ID | 15105289 | Mgi Jnum | J:92963 |
| Mgi Id | MGI:3055260 | Doi | 10.1182/blood-2003-10-3428 |
| Citation | Chen J, et al. (2004) Impaired platelet responses to thrombin and collagen in AKT-1-deficient mice. Blood 104(6):1703-10 |
| abstractText | 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. |
