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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 (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 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 Social Bookmarking                   What's this? Submitted January 6, 2003 Accepted April 14, 2003 Murine GPVI stimulates weak integrin activation in PLC2-/- platelets: involvement of PLC1 and PI 3-kinase Katsue Suzuki-Inoue*, Osamu Inoue, Jon Frampton, and Steve P Watson Department of Pharmacology, University of Oxford, Oxford, United Kingdom Division of Infection and Immunity, The Medical School, University of Birmingham, Birmingham, United Kingdom Division of Medical Sciences, The Medical School, University of Birmingham, Birmingham, United Kingdom * Corresponding author; email: katsue.inoue{at}pharm.ox.ac.uk. Collagen stimulates platelet activation through a tyrosine kinase-based pathway downstream of the 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 (PL) 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 two 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 CRP also stimulate 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, tyrosine 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 PI 3-kinase. 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