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Protease-activated receptor 3 is a second thrombin receptor in humans

Nature volume 386, pages 502–506 (1997)Cite this article

Abstract

Thrombin is a coagulation protease that activates platelets, leukocytes, endothelial and mesenchymal cells at sites of vascular injury, acting partly through an unusual proteolytically activated G-protein-coupled receptor1–3. Knockout of the gene encoding this receptor provided definitive evidence for a second thrombin receptor in mouse platelets and for tissue-specific roles for different thrombin receptors4. We now report the cloning and characterization of a new human thrombin receptor, designated protease-activated receptor 3 (PAR3). PAR3 can mediate throm-bin-triggered phosphoinositide hydrolysis and is expressed in a variety of tissues, including human bone marrow and mouse megakaryocytes, making it a candidate for the sought-after second platelet thrombin receptor. PAR3 provides a new tool for understanding thrombin signalling and a possible target for therapeutics designed selectively to block thrombotic, inflammatory and proliferative responses to thrombin.

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Authors and Affiliations

  1. Cardiovascular Research Institute and Daiichi Research Center, Departments of Pathology and Medicine, University of California, San Francisco, HSW-831, 505 Parnassus Avenue, San Francisco, California, 94143-0130, USA

    Hiroaki Ishihara, Andrew J. Connolly, Dewan Zeng, Mark L. Kahn, Yao Wu Zheng, Courtney Timmons, Tracy Tram & Shaun R. Coughlin

  2. Departments of Pathology, University of California, San Francisco, HSW-831, 505 Parnassus Avenue, San Francisco, California, 94143-0130, USA

    Andrew J. Connolly

  3. Departments of Medicine, University of California, San Francisco, HSW-831, 505 Parnassus Avenue, San Francisco, California, 94143-0130, USA

    Shaun R. Coughlin

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  1. Hiroaki Ishihara
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Ishihara, H., Connolly, A., Zeng, D. et al. Protease-activated receptor 3 is a second thrombin receptor in humans. Nature 386, 502–506 (1997). https://doi.org/10.1038/386502a0

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