Proteinase-Activated Receptor 2
PAR2 is a G-protein-coupled receptor which can be activated by trypsin, tryptase, factor VIIa, factor Xa, matriptase (MT-SP1), and proteinase 3. It consists of 397 amino acids (44 kDa) including the amino-terminal signal sequence and is widely expressed in different tissues and upregulated in numerous cancers. The gene maps to 5q13.3 (gene name: F2RL1).
PAR2 is activated by specific proteolysis at the site SKGR36 ↓ S37LIGKV to expose the tethered ligand SLIGKV which binds to the second extracellular loop, thus activating the receptor, resulting in signal transduction. A synthetic peptide (“activating peptide”) that mimics the tethered ligand domain (SLIGKV-NH2) directly binds to and activates PAR2 in vitro without proteolytic cleavage. In vivo, PAR2 can also be stimulated by transactivation through PAR1: the tethered ligand domain of PAR1is able to...