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Prepublished online as a Blood First Edition Paper on July 3, 2003; DOI 10.1182/blood-2003-04-1142. This Article 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 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 Social Bookmarking                   What's this? Submitted April 14, 2003 Accepted May 29, 2003 Tec regulates platelet activation by GPVI in the absence of Btk Ben T Atkinson*, Wilfried Ellmeier, and Steve P Watson Department of Pharmacology, University of Oxford, Oxford, United Kingdom Institute of Immunology, University of Vienna, Vienna, Austria Department of Pharmacology, University of Oxford, Oxford, United Kingdom; Division of Medical Sciences, The Medical School, Birmingham, United Kingdom * Corresponding author; email: ben.atkinson{at}pharm.ox.ac.uk. The Tec family kinase Btk plays an important role in the regulation of PLC2 downstream of the collagen receptor GPVI in human platelets. Platelets also express a second member of this family, Tec, however its function has not been analysed. To address the role of Tec, we analysed Btk-/-, Tec-/- and Btk/Tec double-deficient (Btk-/-/Tec-/-) platelets. Tec-/- platelets exhibit a very minor reduction in aggregation to threshold concentrations of collagen or the GPVI-specific agonist 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 ADP and spread on fibrinogen. A residual GPVI signal exists in the Btk-/-/Tec-/- platelets as CRP synergises 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. 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