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Thrombin-induced platelet activation via PAR4: pivotal role for exosite II
Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
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2014 (English)In: Thrombosis and Haemostasis, ISSN 0340-6245, Vol. 112, no 3, p. 558-565Article in journal (Refereed) Published
Abstract [en]

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 alpha- and gamma-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 Ib alpha.

Place, publisher, year, edition, pages
Stuttgart, Germany: Schattauer Gmbh, 2014. Vol. 112, no 3, p. 558-565
National Category
Medical and Health Sciences Hematology
Research subject
Biomedicine; Cardiology
Identifiers
URN: urn:nbn:se:oru:diva-41366DOI: 10.1160/TH13-12-1013ISI: 000341547000015PubMedID: 24990072Scopus ID: 2-s2.0-84933073798OAI: oai:DiVA.org:oru-41366DiVA, id: diva2:780393
Funder
Swedish Research CouncilSwedish Heart Lung FoundationAvailable from: 2015-01-14 Created: 2015-01-14 Last updated: 2018-06-15Bibliographically approved

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Ramström, SofiaGrenegård, Magnus

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School of Health and Medical Sciences, Örebro University, Sweden
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