SEARCH:   Advanced

Blood, 15 January 2007, Vol. 109, No. 2, pp. 595-602. Prepublished online as a Blood First Edition Paper on September 19, 2006; DOI 10.1182/blood-2005-11-011775. This Article Full Text (PDF) All Versions of this Article: blood-2005-11-011775v1 109/2/595    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 Van de Walle, G. R Articles by Deckmyn, H. Search for Related Content PubMed PubMed Citation Articles by Van de Walle, G. R Articles by Deckmyn, H. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 30, 2005 Accepted August 18, 2006 Activation of IIb3 is a sufficient but also an imperative prerequisite to activate 21 on platelets Gerlinde R Van de Walle, Anne Schoolmeester, Brecht F Iserbyt, Judith M.E.M. Cosemans, Johan W.M. Heemskerk, Marc F. Hoylaerts, Alan Nurden, Karen Vanhoorelbeke, and Hans Deckmyn* Laboratory for Thrombosis Research, K.U. Leuven Campus Kortrijk, Kortrijk, Belgium Departments of Biochemistry and Human Biology, CARIM, Maastricht University, The Netherlands Center for Molecular and Vascular Biology, K.U. Leuven, Leuven, Belgium Institut Federatif #4, Hopital Cardiologique, Pessac, France * Corresponding author; email: hans.deckmyn{at}kulak.ac.be. Platelet integrins 21 and IIb3 play critical roles in platelet adhesion and thrombus formation after vascular injury. On resting platelets, both integrins are in a low affinity state. However, agonist stimulation results in conformational changes that enable ligand binding that can be detected with conformation dependent monoclonal antibodies (mAbs). By using such conformation dependent mAbs, we could demonstrate that activation of integrin IIb3 is not only sufficient, but also a prerequisite for 21 activation. Compared to platelets in plasma, stimulation of washed platelets resulted in only a minor activation of 21, as detected with the activation-sensitive mAb IAC-1. Addition of fibrinogen to stimulated washed platelets greatly potentiated activation of this integrin. Also, treatment of IIb3 with the ligand-mimetic peptide RGDS, resulting in outside-in signaling, led to a powerful 21 activation, even in the absence of overall platelet activation, involving tyrosine kinase activity but no protein kinase C activation. The absolute necessity of IIb3 for proper 21 activation on platelets was demonstrated by using the IIb3 antagonist aggrastat, which was able to completely abolish 21 activation, both under static and flow conditions. Additionally, analogous experiments with Glanzmann platelets, lacking IIb3, confirmed the indispensability of IIb3 for 21 activation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. Mazzucato, M. R. Cozzi, M. Battiston, M. Jandrot-Perrus, M. Mongiat, P. Marchese, T. J. Kunicki, Z. M. Ruggeri, and L. De Marco Distinct spatio-temporal Ca2+ signaling elicited by integrin {alpha}2{beta}1 and glycoprotein VI under flow Blood, September 24, 2009; 114(13): 2793 - 2801. [Abstract] [Full Text] [PDF] J. Rivera, M. L. Lozano, L. Navarro-Nunez, and V. Vicente Platelet receptors and signaling in the dynamics of thrombus formation Haematologica, May 1, 2009; 94(5): 700 - 711. [Abstract] [Full Text] [PDF] N. Prevost, J. V. Mitsios, H. Kato, J. E. Burke, E. A. Dennis, T. Shimizu, and S. J. Shattil Group IVA cytosolic phospholipase A2 (cPLA2{alpha}) and integrin {alpha}IIb{beta}3 reinforce each other's functions during {alpha}IIb{beta}3 signaling in platelets Blood, January 8, 2009; 113(2): 447 - 457. [Abstract] [Full Text] [PDF] D. Varga-Szabo, I. Pleines, and B. Nieswandt Cell Adhesion Mechanisms in Platelets Arterioscler Thromb Vasc Biol, March 1, 2008; 28(3): 403 - 412. [Abstract] [Full Text] [PDF]

	Copyright © 2006 by American Society of Hematology         Online ISSN: 1528-0020