Proteinase-activated receptors

Proteinase-activated Receptors. Figure 1 Activation of proteinase-activated receptors (PARs) through proteolytic cleavage with serine proteinases (1) and independent of cleavage though PAR-specific activating peptides (2). 

Proteinase-activated Receptors. Table 1 Proteinase, peptide and non-peptide modulators of PAR activation... 

Hollenberg MD, Compton SJ (2002) International union of pharmacology. XXVII. Proteinase-activated receptors. Pharmacol Rev 54 203-217... 

MacFarlane SR, Seatter MJ, Kanke T et al (2001) Proteinase-activated receptors. Pharmacol Rev 53 245— 282... 

In some cases, receptor inactivation, e.g., of the V2 vasopressin receptor, is mediated by agonist-induced enzymatic cleavage of the GPCR. This nonendocytic proteolysis is promoted by a plasma membrane-associated metalloprotease. Proteinase-activated receptors (PARs) such as the thrombin receptor also follow a distinctly different pathway. PARs require the enzymatic cleavage of their N terminus, and the newly generated N terminus activates the receptor. Once... 

Trypsin is a major proteolytic digestive enzyme and the identified endogenous ligand for proteinase-activated receptor 2 (PAR 2). 

Moss ML, Jin SL, MiUa ME et al (1997) Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-alpha. Nature 385 733-736 Nixon RA, Cataldo AM (2006) Lysosomal system pathways genes to neurodegeneration in Alzheimer s disease. J Alzheimers Dis 9 277-289 Noorbakhsh F, VergnoUe N, HoUenberg MD et al (2003) Proteinase-activated receptors in the nervous system. Nat Rev Neurosci 4 981-990... 

Another possible mechanism for kallikrein action in physiology and pathobiology is the activation of proteinase-activated receptors (PARs). PAR is a recently described family of G-protein-coupled receptors with seven transmembrane domains that are stimulated by cleavage of their N-termini by a serine protease rather than by ligand-receptor interaction [184-186]. Four PARs have been identified so far, of which PARI, PAR3,... 

Noorbakhsh F, Vergnolle N, Hollenberg MD, Power C. Proteinase-activated receptors in the nervous system. Nat Rev Neurosci 2003 4 981-990. 

Steinhoff, M., Neisius, U., Ikoma, A. et al. Proteinase-activated receptor-2 mediates itch a novel pathway for pruritus in human skin. J. Neurosci. 16, 6176-6180 (2003). 

Coelho AM, Ossovskaya V, Bunnett NW. Proteinase-activated receptor-2 Physiological and pathophysiological roles. Curr Med Chem Cardiovasc Hematol Agents 2003 1 61-72. 

---