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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 (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 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 Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 25, 2005 Accepted June 20, 2005 Botrocetin/vWf-induced signaling through GPIb-IX-V that produces TxA2 in an IIb3 and aggregation-independent manner Junling Liu, Tamara Pestina, Michael C Berndt, Carl W Jackson, and T K Gartner* Department of Biology, University of Memphis, Memphis, TN, USA Division of Experimental Hematology, St. Jude Children's Research Hospital, Memphis, TN, USA Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia * Corresponding author; email: tgartner{at}memphis.edu. 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 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, SLP-76, PLC2, LAT or 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 PKC. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. E. Speich, S. Grgurevich, T. J. Kueter, A. D. Earhart, S. M. Slack, and L. K. Jennings Platelets undergo phosphorylation of Syk at Y525/526 and Y352 in response to pathophysiological shear stress Am J Physiol Cell Physiol, October 1, 2008; 295(4): C1045 - C1054. [Abstract] [Full Text] [PDF] 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. 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