SEARCH:   Advanced

Blood, 15 October 2006, Vol. 108, No. 8, pp. 2596-2603. Prepublished online as a Blood First Edition Paper on June 20, 2006; DOI 10.1182/blood-2006-01-011817. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-01-011817v1 108/8/2596    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 Related Letters in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Bruton tyrosine kinase is essential for botrocetin/VWF-induced signaling and GPIb-dependent thrombus formation in vivo Junling Liu, Malinda E. Fitzgerald, Michael C. Berndt, Carl W. Jackson, and T. Kent Gartner From the Department of Biology, University of Memphis, TN; Department of Biology, Christian Brothers University, Memphis, TN; Department of Anatomy and Neurobiology, University of Tennessee, Memphis; Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia; and Division of Experimental Hematology, St Jude Children's Research Hospital, Memphis, TN. Botrocetin (bt)-facilitated binding of von Willebrand factor (VWF) to the platelet membrane glycoprotein (GP) Ib-IX-V complex on platelets in suspension initiates a signaling cascade that causes IIb3 activation and platelet aggregation. Previous work has demonstrated that bt/VWF-mediated agglutination activates IIb3 and elicits ATP secretion in a thromboxane A2 (TxA2)-dependent manner. The signaling that results in TxA2 production was shown to be initiated by Lyn, enhanced by Src, and propagated through Syk, SLP-76, PI3K, PLC2, and PKC. Here, we demonstrate that the signaling elicited by GPIb-mediated agglutination that results in TxA2 production is dependent on Bruton tyrosine kinase (Btk). The results demonstrate that Btk is downstream of Lyn, Syk, SLP-76, and PI3K; upstream of ERK1/2, PLC2, and PKC; and greatly enhances Akt phosphorylation. The relationship(s), if any, between ERK1/2, PLC2, and PKC were not elucidated. The requirement for Btk and TxA2 receptor function in GPIb-dependent arterial thrombosis was confirmed in vivo by characterizing blood flow in ferric chloride-treated mouse carotid arteries. These results demonstrate that the Btk family kinase, Tec, cannot provide the function(s) missing because of the absence of Btk and that Btk is essential for both bt/VWF-mediated agglutination-induced TxA2 production and GPIb-dependent stable arterial thrombus formation in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Letters in Blood Online: Are Erk, Btk, and PECAM-1 major players in GPIb signaling? The challenge of unraveling signaling events downstream of platelet GPIb Shaun P. Jackson, Susan Cranmer, Pierre Mangin, and Yuping Yuan Blood 2007 109: 846-847. [Full Text] [PDF] Response: Establishing the physiological significance in vivo answers the challenge of unraveling the details of GPIb-initiated signal transduction Junling Liu, Malinda E. C. Fitzgerald, Michael C. Berndt, Carl W. Jackson, and T. Kent Gartner Blood 2007 109: 847-848. [Full Text] [PDF] Response: Is there a physiologically relevant experimental model system to study GP1b-mediated signaling in platelets? Satya P. Kunapuli Blood 2007 109: 848. [Full Text] [PDF] This article has been cited by other articles: 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] S. P. Jackson The growing complexity of platelet aggregation Blood, June 15, 2007; 109(12): 5087 - 5095. [Abstract] [Full Text] [PDF] S. Jain, M. Zuka, J. Liu, S. Russell, J. Dent, J. A. Guerrero, J. Forsyth, B. Maruszak, T. K. Gartner, B. Felding-Habermann, et al. Platelet glycoprotein Ib{alpha} supports experimental lung metastasis PNAS, May 22, 2007; 104(21): 9024 - 9028. [Abstract] [Full Text] [PDF] S. P. Jackson, S. Cranmer, P. Mangin, and Y. Yuan Are Erk, Btk, and PECAM-1 major players in GPIb signaling? The challenge of unraveling signaling events downstream of platelet GPIb Blood, January 15, 2007; 109(2): 846 - 847. [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]

	Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020