Figure 5.

Classical (canonical) and biased (noncanonical) activation of PAR2. (A) Classical: Activation of PAR2, through the proteolytic removal of the N-terminal pro-peptide domain by trypsin and TLPs, unmasks the tethered ligand in order to trigger signalling via G_αq, and calcium flux leads to associated inflammatory responses. (B) Biased: Proteases cleaving downstream of the activation site (e.g., NE and PR-3) disarm the receptor to truncate the tethered ligand, rendering it unavailable for further activation, although the MAPK pathway can still be activated independent of calcium increase and β-arrestin interactions.