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Blood, 1 February 2006, Vol. 107, No. 3, pp. 947-954. Prepublished online as a Blood First Edition Paper on October 13, 2005; DOI 10.1182/blood-2005-07-3040. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-07-3040v1 107/3/947    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 Kim, S. Articles by Kunapuli, S. P. Search for Related Content PubMed PubMed Citation Articles by Kim, S. Articles by Kunapuli, S. P. 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 Relative contribution of G-protein-coupled pathways to protease-activated receptor-mediated Akt phosphorylation in platelets Soochong Kim, Jianguo Jin, and Satya P. Kunapuli From the Departments of Physiology and Pharmacology and the Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA. Protease-activated receptors (PARs) activate Gq and G12/13 pathways, as well as Akt (protein kinase B [PKB/Akt]) in platelets. However, the relative contribution of different G-protein pathways to Akt phosphorylation has not been elucidated. We investigated the contribution of Gq and G12/13 to Gi/Gz-mediated Akt phosphorylation downstream of PAR activation. Selective G12/13 activation failed to cause Akt phosphorylation in human and Gq-deficient mouse platelets. However, supplementing Gi/Gz signaling to G12/13 caused significant increase in Akt phosphorylation, confirming that G12/13 potentiates Akt phosphorylation. Inhibition of PAR-mediated Akt phosphorylation in the presence of the Gq-selective inhibitor YM-254890 was restored to the normal extent achieved by PAR agonists if supplemented with Gi signaling, indicating that Gq does not have any direct effect on Akt phosphorylation. Selective G12/13 activation resulted in Src kinase activation, and Akt phosphorylation induced by costimulation of G12/13 and Gi/Gz was inhibited by a Src kinase inhibitor but not by a Rho kinase inhibitor. These data demonstrate that G12/13, but not Gq, is essential for thrombin-induced Akt phosphorylation in platelets, whereas Gq indirectly contributes to Akt phosphorylation through Gi stimulation by secreted ADP. G12/13 activation might mediate its potentiating effect through Src activation, and Src kinases play an important role in thrombin-mediated Akt phosphorylation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Li, S. August, and D. S. Woulfe GSK3{beta} is a negative regulator of platelet function and thrombosis Blood, April 1, 2008; 111(7): 3522 - 3530. [Abstract] [Full Text] [PDF] S. Kim, A. Garcia, S. P. Jackson, and S. P. Kunapuli Insulin-like growth factor-1 regulates platelet activation through PI3-K{alpha} isoform Blood, December 15, 2007; 110(13): 4206 - 4213. [Abstract] [Full Text] [PDF] R. K. Bowers, P. Marder, L. J. Green, C. L. Horn, A. L. Faber, and J. E. Thomas A platelet biomarker for assessing phosphoinositide 3-kinase inhibition during cancer chemotherapy Mol. Cancer Ther., September 1, 2007; 6(9): 2600 - 2607. [Abstract] [Full Text] [PDF]

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