F2rl1

Summary

Gene Symbol: F2rl1
Description: F2R like trypsin receptor 1
Alias: Par-2, Par2, proteinase-activated receptor 2, Proteinase-activated receptor-2, G protein-coupled receptor 11, coagulation factor II (thrombin) receptor-like 1, coagulation factor II receptor-like 1, thrombin receptor-like 1
Species: rat
Products:     F2rl1

Top Publications

  1. Rallabhandi P, Nhu Q, Toshchakov V, Piao W, Medvedev A, Hollenberg M, et al. Analysis of proteinase-activated receptor 2 and TLR4 signal transduction: a novel paradigm for receptor cooperativity. J Biol Chem. 2008;283:24314-25 pubmed publisher
    Proteinase-activated receptor 2 (PAR2), a seven-transmembrane G protein-coupled receptor, is activated at inflammatory sites by proteolytic cleavage of its extracellular N terminus by trypsin-like enzymes, exposing a tethered, receptor-..
  2. Knecht W, Cottrell G, Amadesi S, Mohlin J, Skåregärde A, Gedda K, et al. Trypsin IV or mesotrypsin and p23 cleave protease-activated receptors 1 and 2 to induce inflammation and hyperalgesia. J Biol Chem. 2007;282:26089-100 pubmed
    ..Thus, trypsin IV and p23 are inhibitor-resistant trypsins that can cleave and activate PARs, causing PAR(1)- and PAR(2)-dependent inflammation and PAR(2)-dependent hyperalgesia. ..
  3. Ferrell W, Lockhart J, Kelso E, Dunning L, Plevin R, Meek S, et al. Essential role for proteinase-activated receptor-2 in arthritis. J Clin Invest. 2003;111:35-41 pubmed
  4. Hughes K, Wijekoon E, Valcour J, Chia E, McGuire J. Effects of chronic in-vivo treatments with protease-activated receptor 2 agonist on endothelium function and blood pressures in mice. Can J Physiol Pharmacol. 2013;91:295-305 pubmed publisher
    Short-term treatments with protease-activated receptor 2-activating peptides (PAR2-AP) induce endothelium-dependent vasodilation and decrease blood pressure...
  5. Stenton G, Nohara O, Déry R, Vliagoftis H, Gilchrist M, Johri A, et al. Proteinase-activated receptor (PAR)-1 and -2 agonists induce mediator release from mast cells by pathways distinct from PAR-1 and PAR-2. J Pharmacol Exp Ther. 2002;302:466-74 pubmed
    ..The responsiveness of mast cells to PAR-AP via a non-PAR-1/non-PAR-2 mechanism complicates the interpretation of in vivo studies using these peptides. ..
  6. Coelho A, Vergnolle N, Guiard B, Fioramonti J, Bueno L. Proteinases and proteinase-activated receptor 2: a possible role to promote visceral hyperalgesia in rats. Gastroenterology. 2002;122:1035-47 pubmed
    ..These results identify a possible role for proteinases and PAR-2 in the genesis of visceral hyperalgesia. ..
  7. Damiano B, Cheung W, Santulli R, Fung Leung W, Ngo K, Ye R, et al. Cardiovascular responses mediated by protease-activated receptor-2 (PAR-2) and thrombin receptor (PAR-1) are distinguished in mice deficient in PAR-2 or PAR-1. J Pharmacol Exp Ther. 1999;288:671-8 pubmed
    ..Moreover, the accentuated response to PAR-1 activation in PAR-2-deficient mice suggests a compensatory response and potential receptor cross-talk. ..
  8. Dai Y, Wang S, Tominaga M, Yamamoto S, Fukuoka T, Higashi T, et al. Sensitization of TRPA1 by PAR2 contributes to the sensation of inflammatory pain. J Clin Invest. 2007;117:1979-87 pubmed
    Proinflammatory agents trypsin and mast cell tryptase cleave and activate PAR2, which is expressed on sensory nerves to cause neurogenic inflammation...
  9. Shpacovitch V, Varga G, Strey A, Gunzer M, Mooren F, Buddenkotte J, et al. Agonists of proteinase-activated receptor-2 modulate human neutrophil cytokine secretion, expression of cell adhesion molecules, and migration within 3-D collagen lattices. J Leukoc Biol. 2004;76:388-98 pubmed
    Proteinase-activated receptor-2 (PAR2) belongs to a novel subfamily of G-protein-coupled receptors with seven-transmembrane domains...

More Information

Publications87

  1. Defea K, Zalevsky J, Thoma M, Dery O, Mullins R, Bunnett N. beta-arrestin-dependent endocytosis of proteinase-activated receptor 2 is required for intracellular targeting of activated ERK1/2. J Cell Biol. 2000;148:1267-81 pubmed
    ..We report that agonists of Galphaq-coupled proteinase-activated receptor 2 (PAR2) stimulate formation of a multiprotein signaling complex, as detected by gel filtration, immunoprecipitation and ..
  2. Kanke T, Macfarlane S, Seatter M, Davenport E, Paul A, McKenzie R, et al. Proteinase-activated receptor-2-mediated activation of stress-activated protein kinases and inhibitory kappa B kinases in NCTC 2544 keratinocytes. J Biol Chem. 2001;276:31657-66 pubmed
    ..This study shows for the first time proteinase-activated receptor-2-mediated stimulation of both SAP kinase and IKK signaling and differing roles for PKC isoforms in the regulation of each pathway. ..
  3. Ricks T, Trejo J. Phosphorylation of protease-activated receptor-2 differentially regulates desensitization and internalization. J Biol Chem. 2009;284:34444-57 pubmed publisher
    Protease-activated receptor 2 (PAR2) is a G protein-coupled receptor irreversibly activated by extracellular proteases...
  4. Huang Z, Tao K, Zhu H, Miao X, Wang Z, Yu W, et al. Acute PAR2 activation reduces GABAergic inhibition in the spinal dorsal horn. Brain Res. 2011;1425:20-6 pubmed publisher
    ..of spinal dorsal horn GABAergic neurotransmission to elucidate the role of protease-activated receptor-2 (PAR2). Initially, we confirmed that PAR2 agonist SL-NH(2) applied intrathecally produced mechanical hyperalgesia...
  5. Miike S, McWilliam A, Kita H. Trypsin induces activation and inflammatory mediator release from human eosinophils through protease-activated receptor-2. J Immunol. 2001;167:6615-22 pubmed
    ..Human eosinophils constitutively transcribe mRNA for PAR2 and PAR3, but not those for PAR1 and PAR4. The expression of PAR2 protein was confirmed by flow cytometry...
  6. Huang Z, Li H, Cowan A, Liu S, Zhang Y, Song X. Chronic compression or acute dissociation of dorsal root ganglion induces cAMP-dependent neuronal hyperexcitability through activation of PAR2. Pain. 2012;153:1426-37 pubmed publisher
    ..Here, we report that protease-activated receptor 2 (PAR2) activation after CCD or dissociation mediates the increase of cAMP activity and protein kinase A (PKA) and cAMP-..
  7. Saifeddine M, Al Ani B, Cheng C, Wang L, Hollenberg M. Rat proteinase-activated receptor-2 (PAR-2): cDNA sequence and activity of receptor-derived peptides in gastric and vascular tissue. Br J Pharmacol. 1996;118:521-30 pubmed
  8. Ge L, Ly Y, Hollenberg M, DeFea K. A beta-arrestin-dependent scaffold is associated with prolonged MAPK activation in pseudopodia during protease-activated receptor-2-induced chemotaxis. J Biol Chem. 2003;278:34418-26 pubmed
  9. Gaca M, Zhou X, Benyon R. Regulation of hepatic stellate cell proliferation and collagen synthesis by proteinase-activated receptors. J Hepatol. 2002;36:362-9 pubmed
    ..This study indicates that the natural proteinase-activated receptor agonists thrombin and MC tryptase might sustain liver fibrosis by promoting stellate cell proliferation and collagen synthesis. ..
  10. Foley J, Conway E. Cross Talk Pathways Between Coagulation and Inflammation. Circ Res. 2016;118:1392-408 pubmed publisher
    ..In this review, we highlight some of the key molecular interactions, some of which are already showing promise as therapeutic targets for inflammatory and thrombotic disorders. ..
  11. Trottier G, Hollenberg M, Wang X, Gui Y, Loutzenhiser K, Loutzenhiser R. PAR-2 elicits afferent arteriolar vasodilation by NO-dependent and NO-independent actions. Am J Physiol Renal Physiol. 2002;282:F891-7 pubmed
    ..These findings indicate that PAR-2 is expressed in the afferent arteriole and that its activation elicits afferent arteriolar vasodilation by NO-dependent and NO-independent mechanisms. ..
  12. Duchesne E, Tremblay M, Cote C. Mast cell tryptase stimulates myoblast proliferation; a mechanism relying on protease-activated receptor-2 and cyclooxygenase-2. BMC Musculoskelet Disord. 2011;12:235 pubmed publisher
    ..Taken together, our data show that tryptase can stimulate myoblast proliferation and this effect is part of a signaling cascade dependent on PAR-2 activation and on the downstream activation of COX-2. ..
  13. Ramachandran R, Eissa A, Mihara K, Oikonomopoulou K, Saifeddine M, Renaux B, et al. Proteinase-activated receptors (PARs): differential signalling by kallikrein-related peptidases KLK8 and KLK14. Biol Chem. 2012;393:421-7 pubmed publisher
    ..Further, we analysed processing by KLK8 vs. KLK14 of synthetic human and rat PAR2-derived sequences representing the cleavage-activation domain of PAR2...
  14. de Madaria E, del Mar Francés M, Gea Sorlí S, Gutierrez L, Viniegra S, Perez Mateo M, et al. Role of protease-activated receptor 2 in lung injury development during acute pancreatitis in rats. Pancreas. 2014;43:895-902 pubmed publisher
    ..The TRP generated during acute pancreatitis could be involved in the progression of lung injury through the activation of PAR-2 in alveolar macrophages. ..
  15. Li J, Kanju P, Patterson M, Chew W, Cho S, Gilmour I, et al. TRPV4-mediated calcium influx into human bronchial epithelia upon exposure to diesel exhaust particles. Environ Health Perspect. 2011;119:784-93 pubmed publisher
    ..The novel concept of air pollution-responsive ciliary signal transduction from PAR-2 to TRPV4 in human respiratory epithelia will accelerate rationally targeted therapies, possibly via the inhalatory route. ..
  16. Alshurafa H, Stenton G, Wallace J, Hollenberg M, Befus A, Vliagoftis H. A protease activated receptor-2 (PAR-2) activating peptide, tc-LIGRLO-NH2, induces protease release from mast cells: role in TNF degradation. BMC Pharmacol. 2004;4:12 pubmed
    ..These data indicate that a PAR-2ap induces the release of proteases from mast cells, which may degrade extracellular cytokines and other substrates thus modulating the inflammatory response. ..
  17. Wang Y, He Y, Wang M, Lv P, Liu J, Wang J. Role of Protease-Activated Receptor 2 in Regulating Focal Segmental Glomerulosclerosis. Cell Physiol Biochem. 2017;41:1147-1155 pubmed publisher
    ..In this report, we examined the role of protease-activated receptors (PARs) subtype PAR2 and its downstream signals in regulating the pathophysiological process of FSGS...
  18. Bao Y, Wang G, Gao Y, Du M, Yang L, Kong X, et al. Topical treatment with Xiaozheng Zhitong Paste alleviates bone cancer pain by inhibiting proteinase-activated receptor 2 signaling pathway. Oncol Rep. 2015;34:1449-59 pubmed publisher
    ..Central sensitization markers such as c-Fos, GFAP, IBA1 and CGRP, as well as proteinase-activated receptor 2 (PAR2) signaling pathway mediators such as PAR2, PKC-γ, PKA and TRPV1, were determined by quantitative RT-PCR and ..
  19. Lee H, Kim H, Kang H, Woo J, Chae S, Lee S, et al. Up-regulation of protease-activated receptor 2 in allergic rhinitis. Ann Otol Rhinol Laryngol. 2007;116:554-8 pubmed
    ..Stronger immunoreactivity for PAR-2 was observed in allergic rhinitis nasal mucosa as compared with normal nasal mucosa. These results suggest that PAR-2 may be involved in allergic nasal inflammation. ..
  20. Liu D, Chen Z, Ge M, Gan X, Hei Z. [Effects of cromolyn sodium on intestinal ischemia-reperfusion injury by inhibiting PAR-2 expression in rats]. Zhonghua Yi Xue Za Zhi. 2012;92:2597-600 pubmed
    ..05). Cromolyn sodium may reduce IIR injury by stabilizing mast cell membrane and inhibiting the expressions of tryptase and PAR-2. ..
  21. Gui Y, Loutzenhiser R, Hollenberg M. Bidirectional regulation of renal hemodynamics by activation of PAR1 and PAR2 in isolated perfused rat kidney. Am J Physiol Renal Physiol. 2003;285:F95-104 pubmed
    ..In the present study, we evaluated the impact of PAR activation on renal hemodynamics using PAR1- and PAR2-activating peptides (TFLLR-NH2 and SLIGRL-NH2) and proteinases (thrombin and trypsin) as PAR agonists in the ..
  22. Banfi C, Brioschi M, Barcella S, Pignieri A, Parolari A, Biglioli P, et al. Tissue factor induction by protease-activated receptor 1 requires intact caveolin-enriched membrane microdomains in human endothelial cells. J Thromb Haemost. 2007;5:2437-44 pubmed
    ..Signaling through PAR1 and PAR2 shifts the endothelium towards a prothrombotic phenotype, thereby exacerbating the initial pathophysiologic ..
  23. Lohman R, Cotterell A, Suen J, Liu L, Do A, Vesey D, et al. Antagonism of protease-activated receptor 2 protects against experimental colitis. J Pharmacol Exp Ther. 2012;340:256-65 pubmed publisher
    ..Here, we investigate whether masking their common target, protease-activated receptor 2 (PAR2), is an effective therapeutic strategy for treating acute and chronic experimental colitis in rats...
  24. Kim Y, Ahn D, Kim M, Joeng J, Chung S. Protease-activated receptor 2 activation inhibits N-type Ca2+ currents in rat peripheral sympathetic neurons. Mol Cells. 2014;37:804-11 pubmed publisher
  25. Russell F, Schuelert N, Veldhoen V, Hollenberg M, McDougall J. Activation of PAR(2) receptors sensitizes primary afferents and causes leukocyte rolling and adherence in the rat knee joint. Br J Pharmacol. 2012;167:1665-78 pubmed publisher
    ..The PAR(2) receptors are involved in chronic arthritis by mechanisms that are as yet unclear. Here, we examined PAR(2) activation in the rat knee joint...
  26. Napoli C, de Nigris F, Cicala C, Wallace J, Caliendo G, Condorelli M, et al. Protease-activated receptor-2 activation improves efficiency of experimental ischemic preconditioning. Am J Physiol Heart Circ Physiol. 2002;282:H2004-10 pubmed
    ..These data support the concept that PAR-2-dependent cell trafficking may regulate signaling responses to cardiac ischemia and inflammation. ..
  27. Fernández Blanco J, Fernández Blanco J, Hollenberg M, Martinez V, Vergara P. PAR-2-mediated control of barrier function and motility differs between early and late phases of postinfectious gut dysfunction in the rat. Am J Physiol Gastrointest Liver Physiol. 2013;304:G390-400 pubmed publisher
    ..A lack of a ketotifen effect suggests no interplay between MCs and PAR-2-mediated motility and ion transport alterations. These observations question the role of MC mediators in PAR-2-modulating postinfectious gut dysfunction. ..
  28. Cho H, Choi J, Yang Y, Hong J, Kim C, Gee H, et al. House dust mite extract activates apical Cl(-) channels through protease-activated receptor 2 in human airway epithelia. J Cell Biochem. 2010;109:1254-63 pubmed publisher
    ..Our results suggest a role for PAR-2 in mucociliary clearance and fluid hypersecretion of airway mucosa in response to air-borne allergens such as HDM. ..
  29. Horie A, Nagai K, Ohkura S, Ohama T, Komatsu H, Sato K. Proinflammatory cytokines suppress the expression level of protease-activated receptor-2 through the induction of iNOS in rat colon. J Vet Med Sci. 2009;71:1609-15 pubmed
    ..These results suggest that suppression of PAR-2 expression under inflammatory conditions is at least partially induced by NO produced in the colonic muscularis externa by proinflammatory cytokines. ..
  30. Kawabata A, Kuroda R, Nishida M, Nagata N, Sakaguchi Y, Kawao N, et al. Protease-activated receptor-2 (PAR-2) in the pancreas and parotid gland: Immunolocalization and involvement of nitric oxide in the evoked amylase secretion. Life Sci. 2002;71:2435-46 pubmed
  31. Namkung W, Yoon J, Kim K, Lee M. PAR2 exerts local protection against acute pancreatitis via modulation of MAP kinase and MAP kinase phosphatase signaling. Am J Physiol Gastrointest Liver Physiol. 2008;295:G886-94 pubmed publisher
    During acute pancreatitis, protease-activated receptor 2 (PAR2) can be activated by interstitially released trypsin...
  32. Luo Y, Wang F, Qin J, Feng M, Lv Y, Wang Q, et al. Long-term downregulation of protease-activated receptor-2 expression in distal colon in rats following bacillary dysentery. Regul Pept. 2010;163:49-56 pubmed publisher
    ..This might be the reason of the low sensitivity of the colon circular muscle strips to the PAR-2-AP-induced relaxation following intragastric administration of S.flexneri. ..
  33. Nhu Q, Shirey K, Teijaro J, Farber D, Netzel Arnett S, Antalis T, et al. Novel signaling interactions between proteinase-activated receptor 2 and Toll-like receptors in vitro and in vivo. Mucosal Immunol. 2010;3:29-39 pubmed publisher
    ..These data support and extend our recently described, novel model of PAR(2)-TLR4 "receptor cooperativity" and highlight the complexity of signaling integration between heterologous innate immune biosensors. ..
  34. Morla L, Crambert G, Mordasini D, Favre G, Doucet A, Imbert Teboul M. Proteinase-activated receptor 2 stimulates Na,K-ATPase and sodium reabsorption in native kidney epithelium. J Biol Chem. 2008;283:28020-8 pubmed publisher
    Proteinase-activated receptors 2 (PAR2) are expressed in kidney, but their function is mostly unknown...
  35. Xing J, Li J. Proteinase-Activated Receptor-2 Sensitivity of Amplified TRPA1 Activity in Skeletal Muscle Afferent Nerves and Exercise Pressor Reflex in Rats with Femoral Artery Occlusion. Cell Physiol Biochem. 2017;44:163-171 pubmed publisher
    ..The purpose of the present study was to determine the role of proteinase-activated receptor-2 (PAR2) in regulating abnormal TRPA1 function and the TRPA1-mediated sympathetic component of the exercise pressor reflex...
  36. Riek Burchardt M, Striggow F, Henrich Noack P, Reiser G, Reymann K. Increase of prothrombin-mRNA after global cerebral ischemia in rats, with constant expression of protease nexin-1 and protease-activated receptors. Neurosci Lett. 2002;329:181-4 pubmed
    ..Thus, control of the balance between the expression of prothrombin and PN-1 may reflect an important mechanism that underlies postischemic thrombin effects. ..
  37. Zoudilova M, Kumar P, Ge L, Wang P, Bokoch G, DeFea K. Beta-arrestin-dependent regulation of the cofilin pathway downstream of protease-activated receptor-2. J Biol Chem. 2007;282:20634-46 pubmed
    ..These findings identify cofilin as a novel target of beta-arrestin-dependent scaffolding and suggest that many PAR-2-induced processes may be independent of Galpha(q/11) protein coupling. ..
  38. Matsuwaki Y, Wada K, White T, Benson L, Charlesworth M, Checkel J, et al. Recognition of fungal protease activities induces cellular activation and eosinophil-derived neurotoxin release in human eosinophils. J Immunol. 2009;183:6708-16 pubmed publisher
    ..Thus, fungal aspartate protease and eosinophil PAR-2 appear critical for the eosinophils' innate immune response to certain fungi, suggesting a novel mechanism for pathologic inflammation in asthma and for host-pathogen interaction...
  39. McLean P, Aston D, Sarkar D, Ahluwalia A. Protease-activated receptor-2 activation causes EDHF-like coronary vasodilation: selective preservation in ischemia/reperfusion injury: involvement of lipoxygenase products, VR1 receptors, and C-fibers. Circ Res. 2002;90:465-72 pubmed
    ..Therefore, we investigated the effects of PAR2 activation on coronary tone in isolated perfused rat hearts and elucidated the mechanisms of any observed effects...
  40. Oikawa M, Saino T, Kimura K, Kamada Y, Tamagawa Y, Kurosaka D, et al. Effects of protease-activated receptors (PARs) on intracellular calcium dynamics of acinar cells in rat lacrimal glands. Histochem Cell Biol. 2013;140:463-76 pubmed publisher
    ..Only PAR2 mRNA was detected in acinar cells of lacrimal glands...
  41. Csernok E, Ai M, Gross W, Wicklein D, Petersen A, Lindner B, et al. Wegener autoantigen induces maturation of dendritic cells and licenses them for Th1 priming via the protease-activated receptor-2 pathway. Blood. 2006;107:4440-8 pubmed
    ..Wegener autoantigen interacts with a "gateway" receptor (PAR-2) on iDCs in vitro triggering their maturation and licenses them for a T helper 1 (Th1)-type response potentially favoring granuloma formation in WG. ..
  42. Sokolova E, Aleshin S, Reiser G. Expression of protease-activated receptor (PAR)-2, but not other PARs, is regulated by inflammatory cytokines in rat astrocytes. Neurochem Int. 2012;60:276-85 pubmed publisher
    ..These findings provide new information about the regulation of expression of PAR subtypes in brain cells. This is of importance for targeting PARs, especially PAR-2, for the treatment of CNS disorders. ..
  43. Siegbahn A, Johnell M, Nordin A, Aberg M, Velling T. TF/FVIIa transactivate PDGFRbeta to regulate PDGF-BB-induced chemotaxis in different cell types: involvement of Src and PLC. Arterioscler Thromb Vasc Biol. 2008;28:135-41 pubmed
    ..Similar behavior of 3 principally different cell types in our experimental setup may reflect a general function of TF in regulation of cell migration. ..
  44. Li R, Rohatgi T, Hanck T, Reiser G. Alpha A-crystallin and alpha B-crystallin, newly identified interaction proteins of protease-activated receptor-2, rescue astrocytes from C2-ceramide- and staurosporine-induced cell death. J Neurochem. 2009;110:1433-44 pubmed publisher
    ..Thus, both PAR-2 and alpha-crystallins are involved in cytoprotection in astrocytes. ..
  45. Bhatt D, Ploug K, Ramachandran R, Olesen J, Gupta S. Activation of PAR-2 elicits NO-dependent and CGRP-independent dilation of the dural artery. Headache. 2010;50:1017-30 pubmed publisher
    ..As PAR-2 is present throughout trigeminovasuclar axis, it may have a role in migraine pathogenesis, independent of CGRP and mast cell mediated mechanism. ..
  46. Hocherl K, Gerl M, Schweda F. Proteinase-activated receptors 1 and 2 exert opposite effects on renal renin release. Hypertension. 2011;58:611-8 pubmed publisher
    ..The PAR2-activating peptide SLIGRL concentration dependently increased RSR and perfusate flow...
  47. Chen M, Lu B, Chen H, Zhang S. [Relationship of protease-activated receptor-2 and mast cell in the rat model of small intestinal mucosal damage by short-term administration of non-steroidal anti-inflammatory drug]. Zhonghua Yi Xue Za Zhi. 2011;91:1502-5 pubmed
    ..PAR-2 may be activated by tryptase released from mast cells and participate in the pathogenesis of small intestinal injury as induced by non-steroidal anti-inflammatory drugs. ..
  48. Wang Y, Luo W, Reiser G. Proteinase-activated receptor-1 and -2 induce the release of chemokine GRO/CINC-1 from rat astrocytes via differential activation of JNK isoforms, evoking multiple protective pathways in brain. Biochem J. 2007;401:65-78 pubmed
    ..This provides new functional insights into PAR/JNK signalling and the protective actions of PARs in brain. ..
  49. Jiang R, Zatta A, Kin H, Wang N, Reeves J, Mykytenko J, et al. PAR-2 activation at the time of reperfusion salvages myocardium via an ERK1/2 pathway in in vivo rat hearts. Am J Physiol Heart Circ Physiol. 2007;293:H2845-52 pubmed
    ..LY + PAR-2 AP, 38 +/- 3%; P > 0.05). Therefore, PAR-2 activation is cardioprotective in the in vivo rat heart ischemia-reperfusion model, and this protection involves the ERK1/2 pathway and PKC. ..
  50. Luo W, Wang Y, Reiser G. p24A, a type I transmembrane protein, controls ARF1-dependent resensitization of protease-activated receptor-2 by influence on receptor trafficking. J Biol Chem. 2007;282:30246-55 pubmed
    ..These findings identify a new function of p24A as a regulator of signal-dependent trafficking that regulates the life cycle of PAR-2, Thus, we reveal a new molecular mechanism underlying resensitization of PAR-2. ..
  51. Dores M, Chen B, Lin H, Soh U, Paing M, Montagne W, et al. ALIX binds a YPX(3)L motif of the GPCR PAR1 and mediates ubiquitin-independent ESCRT-III/MVB sorting. J Cell Biol. 2012;197:407-19 pubmed publisher
    ..This study reveals a novel MVB/lysosomal sorting pathway for signaling receptors that bypasses the requirement for ubiquitination and ubiquitin-binding ESCRTs and may be applicable to a subset of GPCRs containing YPX(n)L motifs. ..
  52. He R, Tang X, Zhang B, Li X, Hong M, Chen Q, et al. Protease-activated receptor 1 and 2 contribute to angiotensin II-induced activation of adventitial fibroblasts from rat aorta. Biochem Biophys Res Commun. 2016;473:517-23 pubmed publisher
    ..The present study hypothesized that PAR1 and PAR2 are involved in Ang II-induced AF activation and contribute to adventitial remodeling...
  53. Smeda J, McGuire J, Daneshtalab N. Protease-activated receptor 2 and bradykinin-mediated vasodilation in the cerebral arteries of stroke-prone rats. Peptides. 2010;31:227-37 pubmed publisher
    ..Despite the presence of vascular injury, edema, inflammation and the loss of endothelium-dependent bradykinin vasodilation we found no evidence that PAR(2) expression or vascular function was altered in MCA after stroke. ..
  54. Sharma R, Prasad V, McCarthy E, Savin V, Dileepan K, Stechschulte D, et al. Chymase increases glomerular albumin permeability via protease-activated receptor-2. Mol Cell Biochem. 2007;297:161-9 pubmed
    ..MCC may also play a role in renal scarring. We propose that inhibiting MCC activity or blocking the activation of PAR-2 may provide new targets for therapy in renal diseases. ..
  55. Aman M, Hirano M, Kanaide H, Hirano K. Upregulation of proteinase-activated receptor-2 and increased response to trypsin in endothelial cells after exposure to oxidative stress in rat aortas. J Vasc Res. 2010;47:494-506 pubmed publisher
    ..This study provides the first evidence that oxidative stress upregulates PAR? in endothelial cells, thereby enhancing the endothelium-dependent relaxant response to PAR? agonists in rat aortas. ..
  56. Dux M, Rosta J, Santha P, Jancso G. Involvement of capsaicin-sensitive afferent nerves in the proteinase-activated receptor 2-mediated vasodilatation in the rat dura mater. Neuroscience. 2009;161:887-94 pubmed publisher
    ..The results indicate that the PAR-2-mediated activation and sensitization of meningeal capsaicin-sensitive C-fiber nociceptors may be significantly implicated in the pathophysiology of headaches. ..
  57. Suckow S, Caudle R. NMDA receptor subunit expression and PAR2 receptor activation in colospinal afferent neurons (CANs) during inflammation induced visceral hypersensitivity. Mol Pain. 2009;5:54 pubmed publisher
    ..afferent neurons (CANs), co-localize with the NR1 and NR2D subunits of the NMDA receptor as well as with the PAR2 receptor...
  58. Kim Y, Chung S, Lee Y, Kim E, Ahn D. Increase of L-type Ca2+ current by protease-activated receptor 2 activation contributes to augmentation of spontaneous uterine contractility in pregnant rats. Biochem Biophys Res Commun. 2012;418:167-72 pubmed publisher
  59. Helyes Z, Sandor K, Borbely E, Tékus V, Pinter E, Elekes K, et al. Involvement of transient receptor potential vanilloid 1 receptors in protease-activated receptor-2-induced joint inflammation and nociception. Eur J Pain. 2010;14:351-8 pubmed publisher
    ..Although intraplantar PAR-2 activation-induced oedema is also TRPV1 receptor-mediated, primary mechanical hyperalgesia, impaired weight distribution and IL-1beta production are independent of this channel. ..
  60. Feld M, Shpacovitch V, Ehrhardt C, Kerkhoff C, Hollenberg M, Vergnolle N, et al. Agonists of proteinase-activated receptor-2 enhance IFN-gamma-inducible effects on human monocytes: role in influenza A infection. J Immunol. 2008;180:6903-10 pubmed
    ..This effect could be associated with the ability of PAR(2) agonists to enhance IFN-gamma-induced protective effects on human monocytes. ..
  61. Rohatgi T, Sedehizade F, Sabel B, Reiser G. Protease-activated receptor subtype expression in developing eye and adult retina of the rat after optic nerve crush. J Neurosci Res. 2003;73:246-54 pubmed
    ..PAR upregulation because of nerve crush in the mild trauma model could act as an effector of early cell death. Eventual return of receptor mRNA to basal levels is consistent with neuroprotection. ..
  62. Yoshida N, Takagi T, Isozaki Y, Suzuki T, Ichikawa H, Yoshikawa T. Proinflammatory role of protease-activated receptor-2 in intestinal ischemia/reperfusion injury in rats. Mol Med Rep. 2011;4:81-6 pubmed publisher
    ..Pre-treatment with anti-rat PCS antibody significantly inhibited the increases in these parameters. These results suggest that PAR-2 plays an important role in the pathogenesis of ischemia/reperfusion-induced intestinal injury. ..
  63. Belghiti M, Estévez Herrera J, Giménez Garzó C, Gonzalez Usano A, Montoliu C, Ferrer Montiel A, et al. Potentiation of the transient receptor potential vanilloid 1 channel contributes to pruritogenesis in a rat model of liver disease. J Biol Chem. 2013;288:9675-85 pubmed publisher
    ..contribution of histaminergic/serotonergic receptors, but significant activation of protein-activated receptor 2 (PAR2) receptors, prostaglandin PGE2 formation, and potentiation of transient receptor potential vanilloid 1 (TRPV1) ..
  64. Bao Y, Hua B, Hou W, Shi Z, Li W, Li C, et al. Involvement of protease-activated receptor 2 in nociceptive behavior in a rat model of bone cancer. J Mol Neurosci. 2014;52:566-76 pubmed publisher
    ..Protease-activated receptor 2 (PAR2), a receptor for inflammatory proteases, has been implicated in nociceptive signaling under both normal and ..
  65. Li S, Guan J, Ge M, Huang P, Lin Y, Gan X. Intestinal mucosal injury induced by tryptase-activated protease-activated receptor 2 requires β-arrestin-2 in vitro. Mol Med Rep. 2015;12:7181-7 pubmed publisher
    ..These data indicate that tryptase may directly damage IEC‑6 cells via PAR-2 and the downstream activation of ERK, and demonstrate that the signaling pathway requires β-arrestin-2. ..
  66. Khoufache K, LeBouder F, Morello E, Laurent F, Riffault S, Andrade Gordon P, et al. Protective role for protease-activated receptor-2 against influenza virus pathogenesis via an IFN-gamma-dependent pathway. J Immunol. 2009;182:7795-802 pubmed publisher
    ..Collectively, these results showed that PAR(2) plays a protective role during IAV infection through IFN-gamma production and decreased excessive recruitment of inflammatory cells to lung alveoli. ..
  67. Lourbakos A, Potempa J, Travis J, D Andrea M, Andrade Gordon P, Santulli R, et al. Arginine-specific protease from Porphyromonas gingivalis activates protease-activated receptors on human oral epithelial cells and induces interleukin-6 secretion. Infect Immun. 2001;69:5121-30 pubmed
    ..gingivalis might mediate inflammatory events associated with periodontal disease on first contact with a primary barrier of cells. ..
  68. Jesmin S, Shimojo N, Yamaguchi N, Mowa C, Oki M, Zaedi S, et al. Effects of protease activated receptor (PAR)2 blocking peptide on endothelin-1 levels in kidney tissues in endotoxemic rat mode. Life Sci. 2014;102:127-33 pubmed publisher
    ..necrosis factor (TNF)-? in kidney tissue in lipopolysaccharide (LPS)-induced septic rat model and the effects of PAR2 blocking peptide on the LPS-induced elevations of renal ET-1 and TNF-? levels. ..
  69. Jesmin S, Gando S, Zaedi S, Prodhan S, Sawamura A, Miyauchi T, et al. Protease-activated receptor 2 blocking peptide counteracts endotoxin-induced inflammation and coagulation and ameliorates renal fibrin deposition in a rat model of acute renal failure. Shock. 2009;32:626-32 pubmed publisher
    ..These results show that PAR-2 plays a key role in the inflammatory and coagulation process of LPS-induced renal failure; however, PAR-2 inhibition alone does not affect improvement in the renal function. ..
  70. Shpacovitch V, Feld M, Holzinger D, Kido M, Hollenberg M, Levi Schaffer F, et al. Role of proteinase-activated receptor-2 in anti-bacterial and immunomodulatory effects of interferon-? on human neutrophils and monocytes. Immunology. 2011;133:329-39 pubmed publisher
    ..Our findings suggest a potentially protective role of PAR(2) agonists in the anti-microbial defence established by human monocytes and neutrophils. ..
  71. Bae J, Yang L, Rezaie A. Factor X/Xa elicits protective signaling responses in endothelial cells directly via PAR-2 and indirectly via endothelial protein C receptor-dependent recruitment of PAR-1. J Biol Chem. 2010;285:34803-12 pubmed publisher
    ..These results suggest that a cross-talk between EPCR and an unknown FX/FXa receptor, which does not require interaction with the Gla domain of FX, recruits PAR-1 to protective signaling pathways in endothelial cells. ..
  72. Sharma N, Kumar R, Renaux B, Saifeddine M, Nishikawa S, Mihara K, et al. Implantation serine proteinase 1 exhibits mixed substrate specificity that silences signaling via proteinase-activated receptors. PLoS ONE. 2011;6:e27888 pubmed publisher
    ..We observed that ISP1 silenced enzyme-triggered PAR signaling by receptor-disarming. This PAR-disarming action of ISP1 may be important for embryo development and implantation. ..
  73. Cheng R, Fiez Vandal C, Schlenker O, Edman K, Aggeler B, Brown D, et al. Structural insight into allosteric modulation of protease-activated receptor 2. Nature. 2017;545:112-115 pubmed publisher
    ..Despite sequence homology across the PAR isoforms, discovery of PAR2 antagonists has been less successful, although GB88 has been described as a weak antagonist...
  74. Gan X, Liu D, Huang P, Gao W, Chen X, Hei Z. Mast-cell-releasing tryptase triggers acute lung injury induced by small intestinal ischemia-reperfusion by activating PAR-2 in rats. Inflammation. 2012;35:1144-53 pubmed publisher
    ..Tryptase released from mast cells mediates ALI induced by intestinal ischemia-reperfusion by activating PAR-2 to produce IL-8. ..
  75. Sun G, Stacey M, Schmidt M, Mori L, Mattoli S. Interaction of mite allergens Der p3 and Der p9 with protease-activated receptor-2 expressed by lung epithelial cells. J Immunol. 2001;167:1014-21 pubmed
  76. Namkung W, Han W, Luo X, Muallem S, Cho K, Kim K, et al. Protease-activated receptor 2 exerts local protection and mediates some systemic complications in acute pancreatitis. Gastroenterology. 2004;126:1844-59 pubmed
  77. Tong X, Ding J, Yang J, Liu C, Zhang Y, Li S, et al. [The effect of protease-activated receptor2 on rat apoptotic cardiomyocytes underwent ischemia reperfusion injury]. Zhonghua Xin Xue Guan Bing Za Zhi. 2009;37:832-6 pubmed
    ..PAR-2 agonist SLIGRL-NH2 could reduce myocardial apoptosis by upregulating the Bcl-2 and PAR-2 mRNA level and downregulating Bax expression in a dose-dependent manner in this rat I/R model. ..
  78. Wang X, Hollenberg M, Loutzenhiser R. Redundant signaling mechanisms contribute to the vasodilatory response of the afferent arteriole to proteinase-activated receptor-2. Am J Physiol Renal Physiol. 2005;288:F65-75 pubmed