Encyclopedia of Signaling Molecules

Living Edition
| Editors: Sangdun Choi

Proteinase-Activated Receptors (PARs)

  • Roland Kaufmann
  • Utz Settmacher
  • Hendrik Ungefroren
Living reference work entry
DOI: https://doi.org/10.1007/978-1-4614-6438-9_101885-1


Neutrophil Elastase Tethered Ligand Lysosomal Target Lipid Raft Integrity Parasite Cysteine Proteinase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.


  1. Adams MN, Ramachandran R, Yau MK, Suen JY, Fairlie DP, Hollenberg MD, Hooper JD. Structure, function and pathophysiology of protease activated receptors. Pharmacol Ther. 2011;130:248–82.CrossRefPubMedGoogle Scholar
  2. Alexander SP, Mathie A, Peters JA. Guide to Receptors and Channels (GRAC), 3rd edition. Br J Pharmacol. 2008;153(Suppl 2):S1–209.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Cunningham M, McIntosh K, Bushell T, Sloan G, Plevin R. Proteinase-activated receptors (PARs) as targets for antiplatelet therapy. Biochem Soc Trans. 2016;44:606–12.CrossRefPubMedGoogle Scholar
  4. Franchi F, Angiolillo DJ. Novel antiplatelet agents in acute coronary syndrome. Nat Rev Cardiol. 2015;12:30–47.CrossRefPubMedGoogle Scholar
  5. Gieseler F, Ungefroren H, Settmacher U, Hollenberg MD, Kaufmann R. Proteinase-activated receptors (PARs) – focus on receptor-receptor-interactions and their physiological and pathophysiological impact. Cell Commun Signal. 2013;11:86.CrossRefPubMedPubMedCentralGoogle Scholar
  6. Hollenberg MD, Compton S. International Union of Pharmacology. XXVIII. Proteinase-activated receptors. Pharmacol Rev. 2002;54:203–17.CrossRefPubMedGoogle Scholar
  7. Hollenberg MD, Mihara K, Polley D, Suen JY, Han A, Fairlie DP, Ramachandran R. Biased signaling and proteinase-activated receptors (PARs): targeting inflammatory disease. Br J Pharmacol. 2014;171:1180–94.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Macfarlane SR, Seatter MJ, Kanke T, Hunter GD, Plevin R. Proteinase-activated receptors. Pharmacol Rev. 2001;53:245–82.PubMedGoogle Scholar
  9. Nakanishi-Matsui M, Zheng YW, Sulciner DJ, Weiss EJ, Ludeman MJ, Coughlin SR. PAR3 is a cofactor for PAR4 activation by thrombin. Nature. 2000;404:609–13.CrossRefPubMedGoogle Scholar
  10. Ossovskaya V, Bunnett N. Protease-activated receptors: contribution to physiology and disease. Physiol Rev. 2004;84:579–621.CrossRefPubMedGoogle Scholar
  11. Ramachandran R, Hollenberg M. Proteinases and signaling: pathophysiological and therapeutic implications via PARs and more. Br J Pharmacol. 2008;153(Suppl 1):S263–82.PubMedGoogle Scholar
  12. Ramachandran R, Mihara K, Chung H, Renaux B, Lau CS, Muruve DA, DeFea KA, Bouvier M, Hollenberg MD. Neutrophil elastase acts as a biased agonist for proteinase-activated receptor-2 (PAR2). J Biol Chem. 2011;286:24638–48.CrossRefPubMedPubMedCentralGoogle Scholar
  13. Ramachandran R, Noorbakhsh F, Defea K, Hollenberg MD. Targeting proteinase-activated receptors: therapeutic potential and challenges. Nat Rev Drug Discov. 2012;11:69–86.CrossRefPubMedGoogle Scholar
  14. Rasmussen UB, Vouret-Craviari V, Jallat S, Schlesinger Y, Pagès G, Pavirani A, Lecocq JP, Pouysségur J, Van Obberghen-Schilling E. cDNA cloning and expression of a hamster alpha-thrombin receptor coupled to Ca2+ mobilization. FEBS Lett. 1991;288:123–8.CrossRefPubMedGoogle Scholar
  15. Russo A, Soh UJ, Trejo J. Proteases display biased agonism at protease-activated receptors: location matters! Mol Interv. 2009;9:87–96.CrossRefPubMedPubMedCentralGoogle Scholar
  16. Scarborough RM, Naughton MA, Teng W, Hung DT, Rose J, Vu TK, Wheaton VI, Turck CW, Coughlin SR. Tethered ligand agonist peptides. Structural requirements for thrombin receptor activation reveal mechanism of proteolytic unmasking of agonist function. J Biol Chem. 1992;267:13146–9.PubMedGoogle Scholar
  17. Steinhoff M, Buddenkotte J, Shpacovitch V, Rattenholl A, Moormann C, Vergnolle N, Luger T, Hollenberg M. Proteinase-activated receptors: transducers of proteinase-mediated signaling in inflammation and immune response. Endocr Rev. 2005;26:1–43.CrossRefPubMedGoogle Scholar
  18. Vu T, Hung D, Wheaton V, Coughlin S. Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell. 1991;64:1057–68.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media LLC 2016

Authors and Affiliations

  • Roland Kaufmann
    • 1
  • Utz Settmacher
    • 1
  • Hendrik Ungefroren
    • 2
  1. 1.Department of General, Visceral and Vascular SurgeryJena University HospitalJenaGermany
  2. 2.University of LübeckLübeckGermany