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. 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. We now report the cloning and characterization of a new human thrombin receptor, designated protease-activated receptor 3 (PAR3). PAR3 can mediate thrombin-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.
Ishihara
H
H
Cardiovascular Research Institute, University of California, San Francisco 94143-0130, USA.
Connolly
A J
AJ
Zeng
D
D
Kahn
M L
ML
Zheng
Y W
YW
Timmons
C
C
Tram
T
T
Coughlin
S R
SR
D000595:Amino Acid Sequence; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D019556:COS Cells; D003001:Cloning, Molecular; D018076:DNA, Complementary; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D009154:Mutation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018179:Receptors, Thrombin / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013917:Thrombin / Q000378:metabolism; D014018:Tissue Distribution
D018076:DNA, Complementary; D012333:RNA, Messenger; D018179:Receptors, Thrombin; C105295:protease-activated receptor 3; D010450:Endopeptidases; D013917:Thrombin