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

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 receptor 1–3 . Knockout of the gene encoding this receptor provided definitive evidence...

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Veröffentlicht in:Nature (London) 1997-04, Vol.386 (6624), p.502-506
Hauptverfasser: Ishihara, Hiroaki, Connolly, Andrew J., Zeng, Dewan, Kahn, Mark L., Wu Zheng, Yao, Timmons, Courtney, Tram, Tracy, Coughlin, Shaun R.
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container_end_page 506
container_issue 6624
container_start_page 502
container_title Nature (London)
container_volume 386
creator Ishihara, Hiroaki
Connolly, Andrew J.
Zeng, Dewan
Kahn, Mark L.
Wu Zheng, Yao
Timmons, Courtney
Tram, Tracy
Coughlin, Shaun R.
description 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 receptor 1–3 . 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 receptors 4 . 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.
doi_str_mv 10.1038/386502a0
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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 receptors 4 . 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.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>9087410</pmid><doi>10.1038/386502a0</doi><tpages>5</tpages></addata></record>
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subjects Amino Acid Sequence
Animals
Biological and medical sciences
Blood coagulation. Blood cells
Blood Platelets - metabolism
Bone marrow
Cloning
Cloning, Molecular
COS Cells
DNA, Complementary
Endopeptidases - metabolism
Fundamental and applied biological sciences. Psychology
General aspects, investigation methods, hemostasis, fibrinolysis
Humanities and Social Sciences
Humans
Hydrolysis
letter
Medical research
Mice
Mice, Inbred C57BL
Molecular and cellular biology
Molecular Mimicry
Molecular Sequence Data
multidisciplinary
Mutation
Rats
Receptors, Thrombin - genetics
Receptors, Thrombin - metabolism
RNA, Messenger - metabolism
Science
Science (multidisciplinary)
Sequence Homology, Amino Acid
Signal Transduction
Thrombin - metabolism
Tissue Distribution
title Protease-activated receptor 3 is a second thrombin receptor in humans
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