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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 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 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 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. Related Collections Cell Adhesion and Motility Signal Transduction Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Activation of IIbß3 is a sufficient but also an imperative prerequisite for activation of 2ß1 on platelets Gerlinde R. Van de Walle1, Anne Schoolmeester1, Brecht F. Iserbyt1, Judith M. E. M. Cosemans2, Johan W. M. Heemskerk2, Marc F. Hoylaerts3, Alan Nurden4, Karen Vanhoorelbeke1, and Hans Deckmyn1, 1 Laboratory for Thrombosis Research, Katholieke Universiteit (KU) Leuven, Campus Kortrijk, Belgium; 2 Departments of Biochemistry and Human Biology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, The Netherlands; 3 Center for Molecular and Vascular Biology, KU Leuven, Belgium; 4 Institut Fédératif No. 4, Hôpital Cardiologique, Pessac, France Platelet integrins 2ß1 and IIbß3 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 IIbß3 is not only sufficient, but also a prerequisite for 2ß1 activation. Compared with platelets in plasma, stimulation of washed platelets resulted in only a minor activation of 2ß1, 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 IIbß3 with the ligand-mimetic peptide RGDS, resulting in outside-in signaling, led to a powerful 2ß1 activation, even in the absence of overall platelet activation, involving tyrosine kinase activity but no protein kinase C activation. The absolute necessity of IIbß3 for proper 2ß1 activation on platelets was demonstrated by using the IIbß3 antagonist aggrastat, which was able to completely abolish 2ß1 activation, both under static and flow conditions. In addition, analogous experiments with Glanzmann platelets lacking IIbß3 confirmed the indispensability of IIbß3 for 2ß1 activation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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]

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