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Blood, 15 October 2005, Vol. 106, No. 8, pp. 2750-2756. Prepublished online as a Blood First Edition Paper on June 28, 2005; DOI 10.1182/blood-2005-04-1667. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-04-1667v1 106/8/2750    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 Liu, J. Articles by Gartner, T. K. Search for Related Content PubMed PubMed Citation Articles by Liu, J. Articles by Gartner, T. K. 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 Botrocetin/VWF-induced signaling through GPIb-IX-V produces TxA2 in an IIb3- and aggregation-independent manner Junling Liu, Tamara I. Pestina, Michael C. Berndt, Carl W. Jackson, and T. Kent Gartner From the Department of Biology, University of Memphis, Memphis, TN; Division of Experimental Hematology, St Jude Children's Research Hospital, Memphis, TN; and Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia. Binding of von Willebrand factor (VWF) to the platelet membrane glycoprotein (GP) Ib-IX-V complex initiates a signaling cascade that causes IIb3 activation and platelet aggregation. Previous work demonstrated that botrocetin (bt)/VWF–mediated agglutination activates IIb3 and elicits adenosine triphosphate (ATP) secretion in a thromboxane A2 (TxA2)– and Ca2+-dependent manner. This agglutination-elicited TxA2 production occurs in the absence of ATP secretion. However, the signaling components and signaling network or pathway activated by GPIb-mediated agglutination to cause TxA2 production have not been identified. Therefore, the focus of this study was to elucidate at least part of the signal transduction network or pathway activated by GPIb-mediated agglutination to cause TxA2 production. The phosphatidylinositol 3-kinase (PI3K) selective inhibitor wortmannin, and mouse platelets deficient in Lyn, Src, Syk, Src homology 2 (SH2) domain–containing leukocyte protein 76 (SLP-76), phospholipase C2 (PLC2), linker for activation of T cells (LAT), or Fc receptor -chain (FcR-chain) were used for these studies. LAT and FcR-chain were found not to be required for agglutination-driven TxA2 production or activation of IIb3, but were required for granule secretion and aggregation. The results also clearly demonstrate that bt/VWF-mediated agglutination-induced TxA2 production is dependent on signaling apparently initiated by Lyn, enhanced by Src, and propagated through Syk, SLP-76, PI3K, PLC2, and protein kinase C (PKC). CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Yin, J. Liu, Z. Li, M. C. Berndt, C. A. Lowell, and X. Du Src family tyrosine kinase Lyn mediates VWF/GPIb-IX-induced platelet activation via the cGMP signaling pathway Blood, August 15, 2008; 112(4): 1139 - 1146. [Abstract] [Full Text] [PDF] F.-T. Mu, R. K. Andrews, J. F. Arthur, A. D. Munday, S. L. Cranmer, S. P. Jackson, F. C. Stomski, A. F. Lopez, and M. C. Berndt A functional 14-3-3{zeta}-independent association of PI3-kinase with glycoprotein Ib{alpha}, the major ligand-binding subunit of the platelet glycoprotein Ib-IX-V complex Blood, May 1, 2008; 111(9): 4580 - 4587. [Abstract] [Full Text] [PDF] H. Yin, A. Stojanovic, N. Hay, and X. Du The role of Akt in the signaling pathway of the glycoprotein Ib-IX induced platelet activation Blood, January 15, 2008; 111(2): 658 - 665. [Abstract] [Full Text] [PDF] J. Liu, M. E. C. Fitzgerald, M. C. Berndt, C. W. Jackson, and T. K. Gartner Response: Establishing the physiological significance in vivo answers the challenge of unraveling the details of GPIb-initiated signal transduction Blood, January 15, 2007; 109(2): 847 - 848. [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] J. Liu, M. E. Fitzgerald, M. C. Berndt, C. W. Jackson, and T. K. Gartner Bruton tyrosine kinase is essential for botrocetin/VWF-induced signaling and GPIb-dependent thrombus formation in vivo Blood, October 15, 2006; 108(8): 2596 - 2603. [Abstract] [Full Text] [PDF] I. C.A. Munnix, A. Strehl, M. J.E. Kuijpers, J. M. Auger, P. E.J. van der Meijden, M. A.M. van Zandvoort, M. G.A. oude Egbrink, B. Nieswandt, and J. W.M. Heemskerk The Glycoprotein VI-Phospholipase C{gamma}2 Signaling Pathway Controls Thrombus Formation Induced by Collagen and Tissue Factor In Vitro and In Vivo Arterioscler. Thromb. Vasc. Biol., December 1, 2005; 25(12): 2673 - 2678. [Abstract] [Full Text] [PDF] A. Garcia, T. M. Quinton, R. T. Dorsam, and S. P. Kunapuli Src family kinase-mediated and Erk-mediated thromboxane A2 generation are essential for VWF/GPIb-induced fibrinogen receptor activation in human platelets Blood, November 15, 2005; 106(10): 3410 - 3414. [Abstract] [Full Text] [PDF]

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