Fig. 1. Activation of protease-activated receptors (PARs) by proteases and by PAR-activating peptides (PAR-APs). The figure illustrates the activation of PARs either by the proteolytic unmasking of the receptor’s N-terminal tethered ligand (left-hand, solid rectangle) or by the addition of a PAR-activating peptide (PAR-AP) based on the sequence of the revealed tethered ligand (right-hand light grey rectangle). PARs 1–4 are believed to couple both to Gq and Gi, to elicit common cellular responses (eg platelet aggregation; cell growth). The tethered ligand peptide sequences for the human PARs are: PAR1, SFLLRN…; PAR2, SLIGKV…; PAR3, TFRGAP… and PAR4, GYPGQV…(Refs 8, 9, 15, 26, 28 and 29).