Protease-activated receptor 4 (PAR-4) belongs to a family of four G protein-coupled receptors (PAR-1 - 4) that are activated as a result of proteolytic cleavage by certain serine proteases, hence their name. In this novel modality of activation, a specific protease cleaves the PAR receptor within a defined sequence in its extracellular N-terminal domain. This results in the creation of a new N-terminal tethered ligand, which subsequently binds to a site in the second extracellular loop of the same receptor. This binding results in the coupling of the receptor to G proteins and in the activation of several signal transduction pathways.1-3
Different PARs are activated by different proteases. Hence, PAR-4 is activated by both thrombin and trypsin whereas PAR-1 and PAR-3 are activated only by thrombin and PAR-2 is activated only by trypsin.1-3 PAR-4 can be also cleaved and activated by other proteases such as cathepsin G.
The intracellular signaling mechanisms mediated by PAR-4 activation are not completely elucidated but they involve calcium mobilization downstream of phospholipase C
