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Blood, 15 November 2005, Vol. 106, No. 10, pp. 3410-3414. Prepublished online as a Blood First Edition Paper on July 14, 2005; DOI 10.1182/blood-2005-05-1933. This Article Full Text (PDF) All Versions of this Article: 2005-05-1933v1 106/10/3410    most recent Alert me when this article is cited Alert me if a correction is posted 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 Garcia, A. Articles by Kunapuli, S. P Search for Related Content PubMed PubMed Citation Articles by Garcia, A. Articles by Kunapuli, S. P Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 12, 2005 Accepted July 8, 2005 Src family kinase and Erk-mediated thromboxane A2 generation is essential for vWf/GPIb-induced fibrinogen receptor activation in human platelets Analia Garcia, Todd M Quinton, Robert T Dorsam, and Satya P Kunapuli* Department of Physiology, Temple University School of Medicine, Philadelphia, PA, USA; Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA, USA Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA, USA Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, USA; Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA, USA Department of Physiology, Temple University School of Medicine, Philadelphia, PA, USA; Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA, USA; Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA, USA * Corresponding author; email: spk{at}temple.edu. The binding of von Willebrand Factor (vWf) to the platelet membrane glycoprotein Ib-IX (GPIb-IX) results in platelet activation. In this study, we sought to clarify previous conflicting reports and elucidate the mechanism of activation and the precise role of Erk in vWf-induced platelet activation. Erk2 is activated in platelets upon stimulation with vWf/ristocetin in a time-dependent manner. vWf-induced Erk2 phosphorylation and TXA2 release were completely blocked by PP2, a Src family kinase inhibitor, suggesting that Erk is downstream of Src family kinases. U73122, a phospholipase C inhibitor, also abolished TXA2 generation and Erk phosphorylation. While vWf fostered agglutination of platelets regardless of any additional treatment, inhibition of MEK with U0126 abolished vWf-induced platelet aggregation and thromboxane production in non-aspirin treated washed platelets. However, in platelets treated with aspirin, vWf failed to cause any aggregation. Thus, we conclude that vWf stimulation of platelets results in phospholipase A2 activation through Erk stimulation, and that Src family kinases and phospholipase C play essential roles in this event. We further conclude that vWf-induced platelet aggregation does not directly depend on Erk activation, but has an absolute requirement for Src/Erk-mediated TXA2 generation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Stefanini, R. C. Roden, and W. Bergmeier CalDAG-GEFI is at the nexus of calcium-dependent platelet activation Blood, September 17, 2009; 114(12): 2506 - 2514. [Abstract] [Full Text] [PDF] B. Nagy Jr, K. Bhavaraju, T. Getz, Y. S. Bynagari, S. Kim, and S. P. Kunapuli Impaired activation of platelets lacking protein kinase C-{theta} isoform Blood, March 12, 2009; 113(11): 2557 - 2567. [Abstract] [Full Text] [PDF] H. Yin, J. Liu, Z. Li, M. C. Berndt, C. A. Lowell, and X. 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[Full Text] [PDF] S. P. Kunapuli Response: Is there a physiologically relevant experimental model system to study GP1b-mediated signaling in platelets? Blood, January 15, 2007; 109(2): 848 - 848. [Full Text] [PDF] A. J. Begonja, J. Geiger, N. Rukoyatkina, S. Rauchfuss, S. Gambaryan, and U. Walter Thrombin stimulation of p38 MAP kinase in human platelets is mediated by ADP and thromboxane A2 and inhibited by cGMP/cGMP-dependent protein kinase Blood, January 15, 2007; 109(2): 616 - 618. [Abstract] [Full Text] [PDF] H. Shankar, B. N. Kahner, J. Prabhakar, P. Lakhani, S. Kim, and S. P. Kunapuli G-protein-gated inwardly rectifying potassium channels regulate ADP-induced cPLA2 activity in platelets through Src family kinases Blood, November 1, 2006; 108(9): 3027 - 3034. [Abstract] [Full Text] [PDF] J. Liu, M. E. Fitzgerald, M. C. Berndt, C. W. Jackson, and T. K. 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