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Prepublished online as a Blood First Edition Paper on May 1, 2003; DOI 10.1182/blood-2003-01-0029. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-01-0029v1 102/4/1367    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 Suzuki-Inoue, K. Articles by Watson, S. P. Search for Related Content PubMed PubMed Citation Articles by Suzuki-Inoue, K. Articles by Watson, 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  Blood, 15 August 2003, Vol. 102, No. 4, pp. 1367-1373 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Murine GPVI stimulates weak integrin activation in PLC2–/– platelets: involvement of PLC1 and PI3-kinase Katsue Suzuki-Inoue, Osamu Inoue, Jon Frampton, and Steve P. Watson From the Department of Pharmacology, University of Oxford, United Kingdom; the Division of Infection and Immunity, The Medical School, University of Birmingham, Edgbaston, United Kingdom; and the Division of Medical Sciences, The Medical School, University of Birmingham, Edgbaston, United Kingdom. Collagen stimulates platelet activation through a tyrosine kinase–based pathway downstream of the glycoprotein VI (GPVI)–Fc receptor (FcR) -chain complex. Genetic ablation of FcR -chain results in a complete inhibition of aggregation to collagen. In contrast, a steady increase in light transmission is induced by collagen in phospholipase C2–deficient (PLC2–/–) platelets in a Born aggregometer, indicating a weak level of activation. This increase is inhibited partially in the presence of an 21-blocking antibody or an IIb3 antagonist and completely by a combination of the 2 inhibitors. It is also abolished by the Src kinase inhibitor PP1 and reduced in the presence of the phosphatidylinositol (PI) 3-kinase inhibitor wortmannin. The GPVI-specific agonists convulxin and collagen-related peptide (CRP) also stimulate weak aggregation in PLC2–/– platelets, which is inhibited by wortmannin and PP1. Collagen and CRP stimulate tyrosine phosphorylation of PLC1 at its regulatory site, Tyr 783, in murine but not in human platelets through a Src kinase–dependent pathway. Adhesion of PLC2–/– platelets to a collagen monolayer is severely reduced at a shear rate of 800 s–1, relative to controls, whereas it is abolished in FcR -chain–/– platelets. These results provide strong evidence that engagement of GPVI stimulates limited integrin activation in PLC2–/– platelets via PLC1 and PI3-kinase. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Suzuki-Inoue, Y. Kato, O. Inoue, M. K. Kaneko, K. Mishima, Y. Yatomi, Y. Yamazaki, H. Narimatsu, and Y. Ozaki Involvement of the Snake Toxin Receptor CLEC-2, in Podoplanin-mediated Platelet Activation, by Cancer Cells J. Biol. Chem., September 7, 2007; 282(36): 25993 - 26001. [Abstract] [Full Text] [PDF] T. Rabie, D. Varga-Szabo, M. Bender, R. Pozgaj, F. Lanza, T. Saito, S. P. Watson, and B. Nieswandt Diverging signaling events control the pathway of GPVI down-regulation in vivo Blood, July 15, 2007; 110(2): 529 - 535. [Abstract] [Full Text] [PDF] G. L. J. Fuller, J. A. E. Williams, M. G. Tomlinson, J. A. Eble, S. L. Hanna, S. Pohlmann, K. Suzuki-Inoue, Y. Ozaki, S. P. Watson, and A. C. Pearce The C-type Lectin Receptors CLEC-2 and Dectin-1, but Not DC-SIGN, Signal via a Novel YXXL-dependent Signaling Cascade J. Biol. Chem., April 27, 2007; 282(17): 12397 - 12409. [Abstract] [Full Text] [PDF] F. Abtahian, N. Bezman, R. Clemens, E. Sebzda, L. Cheng, S. J. Shattil, M. L. Kahn, and G. A. Koretzky Evidence for the Requirement of ITAM Domains but Not SLP-76/Gads Interaction for Integrin Signaling in Hematopoietic Cells. Mol. Cell. Biol., September 1, 2006; 26(18): 6936 - 6949. [Abstract] [Full Text] [PDF] O. Inoue, K. Suzuki-Inoue, O. J. T. McCarty, M. Moroi, Z. M. Ruggeri, T. J. Kunicki, Y. Ozaki, and S. P. Watson Laminin stimulates spreading of platelets through integrin {alpha}6beta1-dependent activation of GPVI Blood, February 15, 2006; 107(4): 1405 - 1412. [Abstract] [Full Text] [PDF] K. 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