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Blood, 15 January 2006, Vol. 107, No. 2, pp. 542-549. Prepublished online as a Blood First Edition Paper on September 20, 2005; DOI 10.1182/blood-2005-05-1994. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-05-1994v1 107/2/542    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  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY A novel Syk-dependent mechanism of platelet activation by the C-type lectin receptor CLEC-2 Katsue Suzuki-Inoue, Gemma L. J. Fuller, Ángel García, Johannes A. Eble, Stefan Pöhlmann, Osamu Inoue, T. Kent Gartner, Sascha C. Hughan, Andrew C. Pearce, Gavin D. Laing, R. David G. Theakston, Edina Schweighoffer, Nicole Zitzmann, Takashi Morita, Victor L. J. Tybulewicz, Yukio Ozaki, and Steve P. Watson From the Department of Clinical and Laboratory Medicine, University of Yamanashi, Japan; Centre for Cardiovascular Sciences, Institute of Biomedical Research, University of Birmingham, United Kingdom; Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, United Kingdom; Institute for Physiological Chemistry and Pathobiochemistry, Muenster University Hospital, Germany; Institute for Clinical and Molecular Virology and Nikolaus-Fiebiger-Center of Molecular Medicine, University of Erlangen-Nürnberg, Erlangen, Germany; Department of Microbiology and Molecular Cell Sciences, University of Memphis, TN; Venom Research Unit, Liverpool School of Tropical Medicine, Liverpool, United Kingdom; Division of Immune Cell Biology, National Institute for Medical Research, London, United Kingdom; and Department of Biochemistry, Meiji Pharmaceutical University, Tokyo, Japan. The snake venom rhodocytin has been reported to bind to integrin 21 and glycoprotein (GP) Ib on platelets, but it is also able to induce activation independent of the 2 receptors and of GPVI. Using rhodocytin affinity chromatography, we have identified a novel C-type lectin receptor, CLEC-2, in platelets that confers signaling responses to rhodocytin when expressed in a cell line. CLEC-2 has a single tyrosine residue in a YXXL motif in its cytosolic tail, which undergoes tyrosine phosphorylation upon platelet activation by rhodocytin or an antibody to CLEC-2, but not to collagen, thrombin receptor agonist peptide (TRAP), or convulxin. Tyrosine phosphorylation of CLEC-2 and other signaling proteins by rhodocytin is inhibited by the Src family kinase inhibitor PP2. Further, activation of murine platelets by rhodocytin is abolished in the absence of Syk and PLC2, and partially reduced in the absence of LAT, SLP-76, and Vav1/Vav3. These findings define a novel signaling pathway in platelets whereby activation of CLEC-2 by rhodocytin leads to tyrosine phosphorylation of its cytosolic tail, binding of Syk and initiation of downstream tyrosine phosphorylation events, and activation of PLC2. CLEC-2 is the first C-type lectin receptor to be found on platelets which signals through this novel pathway. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. J. Kunicki CLEC ... too! Blood, October 15, 2009; 114(16): 3364 - 3365. [Full Text] [PDF] F. May, I. Hagedorn, I. Pleines, M. Bender, T. Vogtle, J. Eble, M. Elvers, and B. Nieswandt CLEC-2 is an essential platelet-activating receptor in hemostasis and thrombosis Blood, October 15, 2009; 114(16): 3464 - 3472. [Abstract] [Full Text] [PDF] A. M. Kerrigan, K. M. Dennehy, D. Mourao-Sa, I. Faro-Trindade, J. A. Willment, P. R. Taylor, J. A. Eble, C. Reis e Sousa, and G. D. Brown CLEC-2 Is a Phagocytic Activation Receptor Expressed on Murine Peripheral Blood Neutrophils J. Immunol., April 1, 2009; 182(7): 4150 - 4157. [Abstract] [Full Text] [PDF] J. Mori, A. C. Pearce, J. C. Spalton, B. Grygielska, J. A. Eble, M. G. Tomlinson, Y. A. Senis, and S. P. Watson G6b-B Inhibits Constitutive and Agonist-induced Signaling by Glycoprotein VI and CLEC-2 J. Biol. Chem., December 19, 2008; 283(51): 35419 - 35427. [Abstract] [Full Text] [PDF] B. Boylan, C. Gao, V. Rathore, J. C. Gill, D. K. Newman, and P. J. Newman Identification of Fc{gamma}RIIa as the ITAM-bearing receptor mediating {alpha}IIb{beta}3 outside-in integrin signaling in human platelets Blood, October 1, 2008; 112(7): 2780 - 2786. [Abstract] [Full Text] [PDF] Y. Nakazawa, S. Sato, M. Naito, Y. Kato, K. Mishima, H. Arai, T. Tsuruo, and N. Fujita Tetraspanin family member CD9 inhibits Aggrus/podoplanin-induced platelet aggregation and suppresses pulmonary metastasis Blood, September 1, 2008; 112(5): 1730 - 1739. [Abstract] [Full Text] [PDF] C. Huysamen, J. A. Willment, K. M. Dennehy, and G. D. Brown CLEC9A Is a Novel Activation C-type Lectin-like Receptor Expressed on BDCA3+ Dendritic Cells and a Subset of Monocytes J. Biol. Chem., June 13, 2008; 283(24): 16693 - 16701. [Abstract] [Full Text] [PDF] 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] 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] C. L. Abram and C. A. Lowell The Expanding Role for ITAM-Based Signaling Pathways in Immune Cells Sci. Signal., March 13, 2007; 2007(377): re2 - re2. [Abstract] [Full Text] [PDF] Y. A. Senis, M. G. Tomlinson, A. Garcia, S. Dumon, V. L. Heath, J. Herbert, S. P. Cobbold, J. C. Spalton, S. Ayman, R. Antrobus, et al. A Comprehensive Proteomics and Genomics Analysis Reveals Novel Transmembrane Proteins in Human Platelets and Mouse Megakaryocytes Including G6b-B, a Novel Immunoreceptor Tyrosine-based Inhibitory Motif Protein Mol. Cell. Proteomics, March 1, 2007; 6(3): 548 - 564. [Abstract] [Full Text] [PDF] A. A. Watson, J. Brown, K. Harlos, J. A. Eble, T. S. Walter, and C. A. O'Callaghan The Crystal Structure and Mutational Binding Analysis of the Extracellular Domain of the Platelet-activating Receptor CLEC-2 J. Biol. Chem., February 2, 2007; 282(5): 3165 - 3172. [Abstract] [Full Text] [PDF] S. C. Hughan, C. E. Hughes, O. J.T. McCarty, E. Schweighoffer, I. Soultanova, J. Ware, V. L.J. Tybulewicz, and S. P. Watson GPVI Potentiation of Platelet Activation by Thrombin and Adhesion Molecules Independent of Src Kinases and Syk Arterioscler Thromb Vasc Biol, February 1, 2007; 27(2): 422 - 429. [Abstract] [Full Text] [PDF] C. Chaipan, E. J. Soilleux, P. Simpson, H. Hofmann, T. Gramberg, A. Marzi, M. Geier, E. A. Stewart, J. Eisemann, A. Steinkasserer, et al. DC-SIGN and CLEC-2 Mediate Human Immunodeficiency Virus Type 1 Capture by Platelets. J. Virol., September 1, 2006; 80(18): 8951 - 8960. [Abstract] [Full Text] [PDF]

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