Thromb Haemost 2014; 112(03): 558-565
DOI: 10.1160/TH13-12-1013
Platelets and Blood Cells
Schattauer GmbH

Thrombin-induced platelet activation via PAR4: pivotal role for exosite II

Niklas Boknäs
1   Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
,
Lars Faxälv
1   Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
,
Daniel Sanchez Centellas
1   Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
,
Maria Wallstedt
1   Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
,
Sofia Ramström
1   Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
,
Magnus Grenegård
2   Department of Clinical Medicine, School of Health Sciences, Örebro University, Örebro, Sweden
,
Tomas L. Lindahl
1   Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden
› Author Affiliations
Financial support: This study was supported by Swedish Research Council projects No K2010–65X-15060–07–3 and K2013–65X-15060–10–3 and the Swedish Heart and Lung Foundation projects No 20100219 and 20120263.
Further Information

Publication History

Received: 12 December 2013

Accepted after major revision: 20 April 2014

Publication Date:
20 November 2017 (online)

Summary

Thrombin-induced platelet activation via PAR1 and PAR4 is an important event in haemostasis. Although the underlying mechanisms responsible for ensuring efficient PAR1 activation by thrombin have been extensively studied, the potential involvement of recognitions sites outside the active site of the protease in thrombin-induced PAR4 activation is largely unknown. In this study, we developed a new assay to assess the importance of exosite I and II for PAR4 activation with α- and γ-thrombin. Surprisingly, we found that exosite II is critical for activation of PAR4. We also show that this dependency on exosite II likely represents a new mechanism, as it is unaffected by blockage of the previously known interaction between thrombin and glycoprotein Ibα.