Figure 1. Activation and signaling of PAR-1.

Thrombin, the most potent activator of PAR-1, binds to the hirudin-like binding domain on the N-terminus of the receptor and proteolytically cleaves between Arg 41 and Ser 42 in an irreversible manner. Ser 42 now acts as a tethered ligand to activate PAR-1. PAR-1 signals through G-protein subtypes, Gα_q, Gα_i, and Gβγ to activate PKC and MAPK, inhibit adenylyl cyclase as well as activate PI3-K and PKB.