Protease activated receptors (PARs) are a distinctive four-member family of seven transmembrane G protein-coupled receptors (GPCRs) widely expressed in inflammatory cells. PARs are cleaved by certain serine proteases to expose a tethered ligand domain, this ligand domain then binds to and activates the receptors to initiate multiple signalling cascades. These PAR-activating proteases therefore represent PAR agonists. This PAR-2 agonist peptide mimics the sequence of the “tethered ligand” and is therefore capable of activating the receptor independently of N-terminal proteolysis.
PAR-3 is required for intercellular adhesion molecule 1 (ICAM-1) expression in endothelial cells and PAR-3 cooperates with PAR-1 to mediate the effect of thrombin on cytokine production and vascular cell adhesion molecule (VCAM-) 1 expression.
PAR activation has been linked to inflammation, therefore compounds that mimic or interfere with the PAR-activating processes are attractive therapeutic candidates
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