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Blood, 15 November 2003, Vol. 102, No. 10, pp. 3592-3599. Prepublished online as a Blood First Edition Paper on July 3, 2003; DOI 10.1182/blood-2003-04-1142. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-04-1142v1 102/10/3592    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 Atkinson, B. T. Articles by Watson, S. P. Search for Related Content PubMed PubMed Citation Articles by Atkinson, B. T. 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 Tec regulates platelet activation by GPVI in the absence of Btk Ben T. Atkinson, Wilfried Ellmeier, and Steve P. Watson From the Department of Pharmacology, University of Oxford, and the Division of Medical Sciences, The Medical School, Birmingham, United Kingdom; and the Institute of Immunology, University of Vienna, Austria. The Tec family kinase Btk plays an important role in the regulation of phospholipase C2 (PLC2) downstream of the collagen receptor glycoprotein VI (GPVI) in human platelets. Platelets also express a second member of this family, Tec; however, its function has not been analyzed. To address the role of Tec, we analyzed Btk-/-, Tec-/-, and Btk/Tec double-deficient (Btk-/-/Tec-/-) platelets. Tec-/- platelets exhibit a minor reduction in aggregation to threshold concentrations of collagen or the GPVI-specific agonist collagen-related peptide (CRP), whereas responses to higher concentrations are normal. Tyrosine phosphorylation of PLC2 by collagen and CRP is not altered in Tec-/- platelets. However, Btk-/-/Tec-/- platelets exhibit a greater reduction in PLC2 phosphorylation than is seen in the absence of Btk, thus revealing an important role for Tec in this situation. Furthermore, Btk-/-/Tec-/- platelets fail to undergo an increase in Ca2+, aggregation, secretion, and spreading in response to collagen or CRP, whereas they aggregate normally to adenosine diphosphate (ADP) and spread on fibrinogen. A residual GPVI signal exists in the Btk-/-/Tec-/- platelets as CRP synergizes with ADP to mediate aggregation. These results demonstrate an essential requirement for Tec and Btk in platelet activation by GPVI and reveal a functional role for Tec in the regulation of PLC2 in the absence of Btk. (Blood. 2003;102: 3592-3599) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. A. Bezman, L. Lian, C. S. Abrams, L. F. Brass, M. L. Kahn, M. S. Jordan, and G. A. Koretzky Requirements of SLP76 tyrosines in ITAM and integrin receptor signaling and in platelet function in vivo J. Exp. Med., August 4, 2008; 205(8): 1775 - 1788. [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] S. C. Hughan, C. E. 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