¹Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, PA 19104, USA

²Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania, PA 19104, USA

³Center for Experimental Therapeutics at the University of Pennsylvania, Philadelphia, Pennsylvania, PA 19104, USA

⁴Istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy

Correspondence to: L F Brass, University of Pennsylvania, Room 913 BRB-II, 421 Curie Blvd., Philadelphia, PA 19104, USA

^aCurrent address: Department of Genetics, University of Pennsylvania, ARC 509, 3516 Civic Center Blvd., Philadelphia PA 19104, USA

^bCurrent address: Department of Medicine, University of Pennsylvania, 952 BRB II/III, 421 Curie Blvd, Philadelphia, PA 19104-6069, USA

^cCurrent address: Departments of Medicine and Pharmacology, Center for Experimental Therapeutics, 913 BRB II/III, 421 Curie Blvd, Philadelphia, PA 19104-6069, USA

The four PAR family members are G protein coupled receptors that are normally activated by proteolytic exposure of an occult tethered ligand. Three of the family members are thrombin receptors. The fourth (PAR2) is not activated by thrombin, but can be activated by other proteases, including trypsin, tryptase and Factor Xa. This review focuses on recent information about the manner in which signaling through these receptors is initiated and terminated, including evidence for inter- as well as intramolecular modes of activation, and continuing efforts to identify additional, biologically-relevant proteases that can activate PAR family members. Oncogene (2001) 20, 1570-1581.

protease-activated receptors; thrombin; platelets; endothelial cells; G proteins; G protein coupled receptors