PAR2 is a member of the large family of 7-transmembrane receptors that couple to guanosine-nucleotide-binding proteins.
PAR2 is also a member of the protease-activated receptor family.
PAR2 is activated by several different endogenous and exogenous proteases.
It is activated by proteolytic cleavage of its extracellular amino terminus between arginine and serine.
The new exposed N-terminus serves as tethered activation ligand, which bind a conserved region on extracellular loop 2 (ECL2) and activates the receptor.
These receptors can also be activated non-protealytically, by exogenous peptide sequences that mimic the final amino acids of the tethered ligand, or by other proteases at cleavage sites that are not related to signaling and that can make them then irresponsive to further protease exposure.
Trypsin is the major PAR2 cleaving protease that initiates inflammatory signaling.
It was found that even thrombin in high concentrations is able to cleave PAR2.
Another PAR2 cleaving protease is tryptase, the main protease of mast cells, which by PAR2 proteolytic cleavage induces calcium signaling and proliferation.
PARs have been identified as substrates of kallikreins, which have been related to various inflammatory and tumorigenic processes.
In case of PAR2, particulary speaking about kallikrein-4, -5, -6 a -14.
PAR2 is a member of the large family of 7-transmembrane receptors that couple to guanosine-nucleotide-binding proteins. PAR2 is also a member of the protease-activated receptor family. PAR2 is activated by several different endogenous and exogenous proteases. It is activated by proteolytic cleavage of its extracellular amino terminus between arginine and serine. The new exposed N-terminus serves as tethered activation ligand, which bind a conserved region on extracellular loop 2 (ECL2) and activates the receptor. These receptors can also be activated non-protealytically, by exogenous peptide sequences that mimic the final amino acids of the tethered ligand, or by other proteases at cleavage sites that are not related to signaling and that can make them then irresponsive to further protease exposure. Trypsin is the major PAR2 cleaving protease that initiates inflammatory signaling. It was found that even thrombin in high concentrations is able to cleave PAR2. Another PAR2 cleaving protease is tryptase, the main protease of mast cells, which by PAR2 proteolytic cleavage induces calcium signaling and proliferation. PARs have been identified as substrates of kallikreins, which have been related to various inflammatory and tumorigenic processes. In case of PAR2, particulary speaking about kallikrein-4, -5, -6 a -14.
Protease-activated receptor 2