Protease-activated receptors (PARs): mechanisms of action and potential therapeutic modulators in PAR-driven inflammatory diseases

Mechanisms of PAR activation. PAR activation is regulated by a direct proteolytic cleavage at the N-terminus, b homo- or heterodimerization with other PARs and transactivation through the cleaved tethered ligand, c compartmentalization on the cell surface, d degradation or recycling by endosomal trafficking, e posttranslational modifications such as glycosylation, phosphorylation, and ubiquitination, and f co-localization with other receptors and cofactor