Protease-activated receptor 3 is a second thrombin receptor in humans
- 1 April 1997
- journal article
- letter
- Published by Springer Science and Business Media LLC in Nature
- Vol. 386 (6624), 502-506
- https://doi.org/10.1038/386502a0
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.Keywords
This publication has 19 references indexed in Scilit:
- Role of the thrombin receptor in development and evidence for a second receptorNature, 1996
- Determinants of Thrombin Receptor Cleavage. RECEPTOR DOMAINS INVOLVED, SPECIFICITY, AND ROLE OF THE P3 ASPARTATEPublished by Elsevier BV ,1995
- Molecular cloning of a potential proteinase activated receptor.Proceedings of the National Academy of Sciences of the United States of America, 1994
- Thrombin receptor function and cardiovascular diseaseTrends in Cardiovascular Medicine, 1994
- Specificity of the thrombin receptor for agonist peptide is defined by its extracellular surfaceNature, 1994
- Crystallographic Structures of Thrombin Complexed with Thrombin Receptor Peptides: Existence of Expected and Novel Binding ModesBiochemistry, 1994
- Domains specifying thrombin–receptor interactionNature, 1991
- Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activationCell, 1991
- The Structure of a Complex of Recombinant Hirudin and Human α-ThrombinScience, 1990
- Regulation of Thrombin Generation and FunctionsSeminars in Thrombosis and Hemostasis, 1988