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Prepublished online as a Blood First Edition Paper on June 14, 2002; DOI 10.1182/blood-2002-03-0812. This Article Full Text (PDF) All Versions of this Article: 2002-03-0812v1 100/7/2499    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 Oury, C. Articles by Hoylaerts, M. F Search for Related Content PubMed PubMed Citation Articles by Oury, C. Articles by Hoylaerts, M. F Social Bookmarking                   What's this? Submitted March 18, 2002 Accepted May 15, 2002 P2X1-mediated activation of extracellular signal-regulated kinase 2 contributes to platelet secretion and aggregation induced by collagen Cecile Oury, Emese Toth-Zsamboki, Jos Vermylen, and Marc F Hoylaerts* Center for Molecular and Vascular Biology, Katholieke Universiteit Leuven, Leuven, Belgium * Corresponding author; email: marc.hoylaerts{at}med.kuleuven.ac.be. ATP and its stable analogue, ,ß-methylene ATP activate the platelet P2X1 ion channel, causing a rapid Ca2+ influx. Here, we show that, in washed apyrase-treated platelets, ,ß-methylene ATP elicits reversible extracellular signal-regulated kinase 2 (ERK2) phosphorylation through a Ca2+-and protein kinase C-dependent pathway. In contrast, HPLC-purified ADP did not trigger ERK2 phosphorylation. ,ß-methylene ATP also activated the ERK2 pathway in P2X1-transfected HEK293 cells but not in cells expressing mutated P2X1delL non-functional channels. Because ATP released from the dense granules during platelet activation contributes to platelet aggregation elicited by low doses of collagen, and because collagen causes ERK2 phosphorylation, we have investigated the role of P2X1-mediated ERK2 activation in these platelet responses. We found that the antagonism of P2X1 with ADP or desensitization of this ion channel with ,ß-methylene ATP both resulted in impaired ERK2 phosphorylation, ATP secretion and platelet aggregation induced by low concentrations of collagen (less or equal to 1 µg/ml), without affecting the minor early dense granule release.Selective MEK1/2 inhibition by U-0126 and Ca2+-chelation with EGTA behaved similarly, whereas PKC inhibition by GF109203-X totally prevented collagen-induced secretion and ERK2 activation. In contrast when elicited by high collagen concentrations (2 µg/ml), platelet aggregation and secretion no longer depended on P2X1 or ERK2 activation, as shown by the lack of their inhibition by ,ß-methylene ATP or U-0126. We thus conclude that mild platelet stimulation with collagen rapidly releases ATP which activates the P2X1-PKC-ERK2 pathway. This process enhances further degranulation of the collagen-primed granules allowing platelet aggregation to be completed. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Grenegard, K. Vretenbrant-Oberg, M. Nylander, S. Desilets, E. G. Lindstrom, A. Larsson, I. Ramstrom, S. Ramstrom, and T. L. Lindahl The ATP-gated P2X1 Receptor Plays a Pivotal Role in Activation of Aspirin-treated Platelets by Thrombin and Epinephrine J. Biol. Chem., July 4, 2008; 283(27): 18493 - 18504. [Abstract] [Full Text] [PDF] A. Kauskot, F. Adam, A. Mazharian, N. Ajzenberg, E. 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