PROTEASE-ACTIVATED RECEPTOR 3 IS A 2ND THROMBIN RECEPTOR IN HUMANS

Thrombin is a coagulation protease that activates platelets, leukocyte s, endothelial and mesenchymal cells at sites of vascular injury, acti ng partly through an unusual proteolytically activated G-protein-coupl ed 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 re ceptor, designated protease-activated receptor 3 (PAR3). PAR3 can medi ate thrombin-triggered phosphoinositide hydrolysis and is expressed in a variety of tissues, including human bone marrow and mouse megakaryo cytes, making it a candidate for the sought-after second platelet thro mbin receptor. PAR3 provides a new tool for understanding thrombin sig nalling and a possible target for therapeutics designed selectively to block thrombotic, inflammatory and proliferative responses to thrombi n.