Protease-activated receptor 2: Difference between revisions
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== Agonists == |
== Agonists == |
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Potent and selective [[small molecule]] [[agonist]]s and [[receptor antagonist|antagonists]] for these receptors have been discovered.<ref name="pmid18768780">{{cite journal | author = Gardell LR, Ma JN, Seitzberg JG, Knapp AE, Schiffer HH, Tabatabaei A, Davis CN, Owens M, Clemons B, Wong KK, Lund B, Nash NR, Gao Y, Lameh J, Schmelzer K, Olsson R, Burstein ES | title = Identification and characterization of novel small-molecule protease-activated receptor 2 agonists | journal = J. Pharmacol. Exp. Ther. | volume = 327 | issue = 3 | pages = 799–808 | year = 2008 | month = December | pmid = 18768780 | doi = 10.1124/jpet.108.142570 }}</ref><ref name="pmid20873792">{{cite journal | author = Barry GD, Suen JY, Le GT, Cotterell A, Reid RC, Fairlie DP | title = Novel agonists and antagonists for human protease activated receptor 2 | journal = J. Med. Chem. | volume = 53 | issue = 20 | pages = 7428–40 | year = 2010 | month = October | pmid = 20873792 | doi = 10.1021/jm100984y }}</ref> |
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==See also== |
==See also== |
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Revision as of 06:30, 15 April 2012
Template:PBB Protease activated receptor 2 (PAR2) also known as coagulation factor II (thrombin) receptor-like 1 (F2RL1) or G-protein coupled receptor 11 (GPR11) is a protein that in humans is encoded by the F2RL1 gene. PAR2 modulates inflammatory responses and acts as a sensor for proteolytic enzymes generated during infection.[1]
Gene
The F2RL1 gene contains two exons and is widely expressed in human tissues. The predicted protein sequence is 83% identical to the mouse receptor sequence.[2]
Mechanism of activation
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. It is activated by trypsin, but not by thrombin. It is activated by proteolytic cleavage of its extracellular amino terminus. The new amino terminus functions as a tethered ligand and activates the receptor. Additionally, these receptors can be activated by exogenous proteases, such as house dust mite protein Der P9.[3] These receptors can also be activated non-protealytically, by exogenous peptide sequences that mimic the final amino acids of the tethered ligand.[4]
Agonists
Potent and selective small molecule agonists and antagonists for these receptors have been discovered.[5][6]
See also
References
- ^ Lee SE, Jeong SK, Lee SH (2010). "Protease and protease-activated receptor-2 signaling in the pathogenesis of atopic dermatitis". Yonsei Med. J. 51 (6): 808–22. doi:10.3349/ymj.2010.51.6.808. PMC 2995962. PMID 20879045.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ "Entrez Gene: F2RL1 coagulation factor II (thrombin) receptor-like 1".
- ^ Sun G, Stacey MA, Schmidt M, Mori L, Mattoli S (2001). "Interaction of mite allergens Der p3 and Der p9 with protease-activated receptor-2 expressed by lung epithelial cells". J. Immunol. 167 (2): 1014–21. PMID 11441110.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Kawabata A, Kanke T, Yonezawa D, Ishiki T, Saka M, Kabeya M, Sekiguchi F, Kubo S, Kuroda R, Iwaki M, Katsura K, Plevin R (2004). "Potent and metabolically stable agonists for protease-activated receptor-2: evaluation of activity in multiple assay systems in vitro and in vivo". J. Pharmacol. Exp. Ther. 309 (3): 1098–107. doi:10.1124/jpet.103.061010. PMID 14976227.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Gardell LR, Ma JN, Seitzberg JG, Knapp AE, Schiffer HH, Tabatabaei A, Davis CN, Owens M, Clemons B, Wong KK, Lund B, Nash NR, Gao Y, Lameh J, Schmelzer K, Olsson R, Burstein ES (2008). "Identification and characterization of novel small-molecule protease-activated receptor 2 agonists". J. Pharmacol. Exp. Ther. 327 (3): 799–808. doi:10.1124/jpet.108.142570. PMID 18768780.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link) - ^ Barry GD, Suen JY, Le GT, Cotterell A, Reid RC, Fairlie DP (2010). "Novel agonists and antagonists for human protease activated receptor 2". J. Med. Chem. 53 (20): 7428–40. doi:10.1021/jm100984y. PMID 20873792.
{{cite journal}}: Unknown parameter|month=ignored (help)CS1 maint: multiple names: authors list (link)
Further reading
- Kunzelmann K, Schreiber R, König J, Mall M (2003). "Ion transport induced by proteinase-activated receptors (PAR2) in colon and airways". Cell Biochem. Biophys. 36 (2–3): 209–14. doi:10.1385/CBB:36:2-3:209. PMID 12139406.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - Kawabata A (2004). "PAR-2: structure, function and relevance to human diseases of the gastric mucosa". Expert reviews in molecular medicine. 4 (16): 1–17. doi:10.1017/S1462399402004799. PMID 14585156.
- Bushell T (2007). "The emergence of proteinase-activated receptor-2 as a novel target for the treatment of inflammation-related CNS disorders". J. Physiol. (Lond.). 581 (Pt 1): 7–16. doi:10.1113/jphysiol.2007.129577. PMC 2075212. PMID 17347265.
- Nystedt S, Emilsson K, Larsson AK; et al. (1995). "Molecular cloning and functional expression of the gene encoding the human proteinase-activated receptor 2". Eur. J. Biochem. 232 (1): 84–9. doi:10.1111/j.1432-1033.1995.tb20784.x. PMID 7556175.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - Santulli RJ, Derian CK, Darrow AL; et al. (1995). "Evidence for the presence of a protease-activated receptor distinct from the thrombin receptor in human keratinocytes". Proc. Natl. Acad. Sci. U.S.A. 92 (20): 9151–5. doi:10.1073/pnas.92.20.9151. PMC 40942. PMID 7568091.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - Nystedt S, Emilsson K, Wahlestedt C, Sundelin J (1994). "Molecular cloning of a potential proteinase activated receptor". Proc. Natl. Acad. Sci. U.S.A. 91 (20): 9208–12. doi:10.1073/pnas.91.20.9208. PMC 44781. PMID 7937743.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - Mirza H, Yatsula V, Bahou WF (1996). "The proteinase activated receptor-2 (PAR-2) mediates mitogenic responses in human vascular endothelial cells". J. Clin. Invest. 97 (7): 1705–14. doi:10.1172/JCI118597. PMC 507235. PMID 8601636.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - Bohm SK, Kong W, Bromme D; et al. (1996). "Molecular cloning, expression and potential functions of the human proteinase-activated receptor-2". Biochem. J. 314 (3): 1009–16. PMC 1217107. PMID 8615752.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - Böhm SK, Khitin LM, Grady EF; et al. (1996). "Mechanisms of desensitization and resensitization of proteinase-activated receptor-2". J. Biol. Chem. 271 (36): 22003–16. doi:10.1074/jbc.271.36.22003. PMID 8703006.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - Kahn M, Ishii K, Kuo WL; et al. (1996). "Conserved structure and adjacent location of the thrombin receptor and protease-activated receptor 2 genes define a protease-activated receptor gene cluster". Mol. Med. 2 (3): 349–57. PMC 2230143. PMID 8784787.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - Molino M, Barnathan ES, Numerof R; et al. (1997). "Interactions of mast cell tryptase with thrombin receptors and PAR-2". J. Biol. Chem. 272 (7): 4043–9. doi:10.1074/jbc.272.7.4043. PMID 9020112.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - Howells GL, Macey MG, Chinni C; et al. (1997). "Proteinase-activated receptor-2: expression by human neutrophils". J. Cell. Sci. 110 (7): 881–7. PMID 9133675.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - D'Andrea MR, Derian CK, Leturcq D; et al. (1998). "Characterization of protease-activated receptor-2 immunoreactivity in normal human tissues". J. Histochem. Cytochem. 46 (2): 157–64. PMID 9446822.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - Guyonnet Dupérat V, Jacquelin B, Boisseau P; et al. (1998). "Protease-activated receptor genes are clustered on 5q13". Blood. 92 (1): 25–31. PMID 9639495.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - Steinhoff M, Corvera CU, Thoma MS; et al. (1999). "Proteinase-activated receptor-2 in human skin: tissue distribution and activation of keratinocytes by mast cell tryptase". Exp. Dermatol. 8 (4): 282–94. doi:10.1111/j.1600-0625.1999.tb00383.x. PMID 10439226.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - Takeuchi T, Harris JL, Huang W; et al. (2000). "Cellular localization of membrane-type serine protease 1 and identification of protease-activated receptor-2 and single-chain urokinase-type plasminogen activator as substrates". J. Biol. Chem. 275 (34): 26333–42. doi:10.1074/jbc.M002941200. PMID 10831593.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - Loew D, Perrault C, Morales M; et al. (2000). "Proteolysis of the exodomain of recombinant protease-activated receptors: prediction of receptor activation or inactivation by MALDI mass spectrometry". Biochemistry. 39 (35): 10812–22. doi:10.1021/bi0003341. PMID 10978167.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - Knight DA, Lim S, Scaffidi AK; et al. (2001). "Protease-activated receptors in human airways: upregulation of PAR-2 in respiratory epithelium from patients with asthma". J. Allergy Clin. Immunol. 108 (5): 797–803. doi:10.1067/mai.2001.119025. PMID 11692107.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - Miike S, McWilliam AS, Kita H (2002). "Trypsin induces activation and inflammatory mediator release from human eosinophils through protease-activated receptor-2". J. Immunol. 167 (11): 6615–22. PMID 11714832.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - Asokananthan N, Graham PT, Fink J; et al. (2002). "Activation of protease-activated receptor (PAR)-1, PAR-2, and PAR-4 stimulates IL-6, IL-8, and prostaglandin E2 release from human respiratory epithelial cells". J. Immunol. 168 (7): 3577–85. PMID 11907122.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link) - Wong, D. M.; Tam, V.; Lam, R.; et al. (2010). "Protease-activated receptor 2 has pivotal roles in cellular mechanisms involved in experimental periodontitis". Infect. Immun. 78 (7): 629–38. PMID 19933835.
{{cite journal}}: Explicit use of et al. in:|author=(help)CS1 maint: multiple names: authors list (link)
External links
- "Protease-Activated Receptors: PAR2". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
{{cite web}}: Cite has empty unknown parameter:|coauthors=(help)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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