|
|
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.
 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:
|
|
|
|
 
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]
|
|
|
|
|
