Protease-activated receptors (PARs) form a family of seven transmembrane G-protein-coupled receptors consisting of four gene members. PAR1, PAR3, and PAR4 respond to the serine protease thrombin, while PAR2 is activated by trypsin, tryptase, and the coagulation factors, VIIa and Xa, but not by thrombin. All members are uniquely activated via proteolytic cleavage that exposes an otherwise hindered ligand at their N-terminus extracellular portion. PARs can be viewed as receptors that carry their own ligands. In addition to thrombin, PARs convey cellular responses to a wide spectrum of serine proteases as also the matrix metalloprotease 1, MMP1. PARs1–4 are similarly organized, all encoded by two exons and separated by an intron of variable size. Exon 1 encodes a signal peptide, and exon 2 encodes the mature receptor protein. In humans, PARs1–3 are localized on chromosome 5q13.
Protease-activated receptors (PARs) belong to the...