| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
(Received for publication, March 28, 1996)
From Recently, a second member of the
protease-activated receptor (PAR) family, named PAR-2, has been
identified. Similar to the thrombin receptor, PAR-2 appears to be
activated by proteolytic-mediated exposure of a ``tethered ligand''
sequence and can also be activated by the corresponding synthetic
peptides. Similarities in the amino acid sequence of the receptors'
tethered ligand sequences suggest that their respective agonist
peptides might not be absolutely specific for their particular
receptors. To test this, the receptor specificity of each agonist has
been determined by measuring the responses of Xenopus
oocytes expressing the thrombin receptor or PAR-2 to agonist peptides
or enzymes. Thrombin receptors responded to thrombin, the human
thrombin receptor-activating peptide SFLLRNP-NH2 (TRAP)
(EC50 = 0.1 µM), and Xenopus
TRAP, TFRIFD-NH2 (EC50 = 1 µM),
but did not show any increase in calcium efflux over control levels
with trypsin (50 nM) or PAR-2 agonist peptides (100 µM). Human and murine PAR-2 receptors responded
comparably to human and murine PAR-2 agonist peptides (SLIGKVD and
SLIGRL, respectively) (EC50 = 0.5-2.0 µM)
and trypsin, but not to thrombin. PAR-2 was also found to be responsive
to TRAP (EC50 = 1 µM) but was unresponsive to
Xenopus TRAP (50 µM). Responses to additional
peptide agonist analogs suggest that an amino-terminal serine is
critical for PAR-2 agonist activity.
Volume 271, Number 28,
Issue of July 12, 1996
pp. 16466-16471
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
,
,
,
,
COR Therapeutics, Inc., South San Francisco,
California 94080 and the ¶ Division of Molecular Neurobiology,
The Wallenberg Laboratory, Lund University,
S-220 07 Lund, Sweden
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  X. Li, T. Syrovets, S. Paskas, Y. Laumonnier, and T. Simmet Mature Dendritic Cells Express Functional Thrombin Receptors Triggering Chemotaxis and CCL18/Pulmonary and Activation-Regulated Chemokine Induction J. Immunol., July 15, 2008; 181(2): 1215 - 1223. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Shpacovitch, M. Feld, M. D. Hollenberg, T. A. Luger, and M. Steinhoff Role of protease-activated receptors in inflammatory responses, innate and adaptive immunity J. Leukoc. Biol., June 1, 2008; 83(6): 1309 - 1322. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Jiang, A. Zatta, H. Kin, N. Wang, J. G. Reeves, J. Mykytenko, J. Deneve, Z.-Q. Zhao, R. A. Guyton, and J. Vinten-Johansen 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, November 1, 2007; 293(5): H2845 - H2852. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Bengrine, J. Li, L. L. Hamm, and M. S. Awayda Indirect Activation of the Epithelial Na+ Channel by Trypsin J. Biol. Chem., September 14, 2007; 282(37): 26884 - 26896. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Knecht, G. S. Cottrell, S. Amadesi, J. Mohlin, A. Skaregarde, K. Gedda, A. Peterson, K. Chapman, M. D. Hollenberg, N. Vergnolle, et al. Trypsin IV or Mesotrypsin and p23 Cleave Protease-activated Receptors 1 and 2 to Induce Inflammation and Hyperalgesia J. Biol. Chem., September 7, 2007; 282(36): 26089 - 26100. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Kirkland, G. S. Cottrell, N. W. Bunnett, and C. U. Corvera Agonists of protease-activated receptors 1 and 2 stimulate electrolyte secretion from mouse gallbladder Am J Physiol Gastrointest Liver Physiol, July 1, 2007; 293(1): G335 - G346. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Cleator, W. Q. Zhu, D. E. Vaughan, and H. E. Hamm Differential regulation of endothelial exocytosis of P-selectin and von Willebrand factor by protease-activated receptors and cAMP Blood, April 1, 2006; 107(7): 2736 - 2744. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. B. Kelso, J. C. Lockhart, T. Hembrough, L. Dunning, R. Plevin, M. D. Hollenberg, C. P. Sommerhoff, J. S. McLean, and W. R. Ferrell Therapeutic Promise of Proteinase-Activated Receptor-2 Antagonism in Joint Inflammation J. Pharmacol. Exp. Ther., March 1, 2006; 316(3): 1017 - 1024. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. N. McLaughlin, L. Shen, M. Holinstat, J. D. Brooks, E. DiBenedetto, and H. E. Hamm Functional Selectivity of G Protein Signaling by Agonist Peptides and Thrombin for the Protease-activated Receptor-1 J. Biol. Chem., July 1, 2005; 280(26): 25048 - 25059. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. N. McLaughlin, M. R. Mazzoni, J. H. Cleator, L. Earls, A. L. Perdigoto, J. D. Brooks, J. A. S. Muldowney III, D. E. Vaughan, and H. E. Hamm Thrombin Modulates the Expression of a Set of Genes Including Thrombospondin-1 in Human Microvascular Endothelial Cells J. Biol. Chem., June 10, 2005; 280(23): 22172 - 22180. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Steinhoff, J. Buddenkotte, V. Shpacovitch, A. Rattenholl, C. Moormann, N. Vergnolle, T. A. Luger, and M. D. Hollenberg Proteinase-Activated Receptors: Transducers of Proteinase-Mediated Signaling in Inflammation and Immune Response Endocr. Rev., February 1, 2005; 26(1): 1 - 43. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Tanaka, T. Morita, A. Nezu, A. Tanimura, I. Mizoguchi, and Y. Tojyo Signaling Mechanisms Involved in Protease-Activated Receptor-1-Mediated Interleukin-6 Production by Human Gingival Fibroblasts J. Pharmacol. Exp. Ther., November 1, 2004; 311(2): 778 - 786. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Koetzner, J. A. Gregory, and T. L. Yaksh Intrathecal Protease-Activated Receptor Stimulation Produces Thermal Hyperalgesia through Spinal Cyclooxygenase Activity J. Pharmacol. Exp. Ther., October 1, 2004; 311(1): 356 - 363. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Shi, B. Gangadharan, L. F. Brass, W. Ruf, and B. M. Mueller Protease-Activated Receptors (PAR1 and PAR2) Contribute to Tumor Cell Motility and Metastasis Mol. Cancer Res., July 1, 2004; 2(7): 395 - 402. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. S. OSSOVSKAYA and N. W. BUNNETT Protease-Activated Receptors: Contribution to Physiology and Disease Physiol Rev, April 1, 2004; 84(2): 579 - 621. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Bolton, C. A. McNulty, R. J. Thomas, C. R. A. Hewitt, and A. J. Wardlaw Expression of and functional responses to protease-activated receptors on human eosinophils J. Leukoc. Biol., July 1, 2003; 74(1): 60 - 68. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. L. Copple, F. Moulin, U. M. Hanumegowda, P. E. Ganey, and R. A. Roth Thrombin and Protease-Activated Receptor-1 Agonists Promote Lipopolysaccharide-Induced Hepatocellular Injury in Perfused Livers J. Pharmacol. Exp. Ther., May 1, 2003; 305(2): 417 - 425. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. McGuire, J. Dai, P. Andrade-Gordon, C. R. Triggle, and M. D. Hollenberg Proteinase-Activated Receptor-2 (PAR2): Vascular Effects of a PAR2-Derived Activating Peptide via a Receptor Different than PAR2 J. Pharmacol. Exp. Ther., December 1, 2002; 303(3): 985 - 992. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Asokananthan, P. T. Graham, D. J. Stewart, A. J. Bakker, K. A. Eidne, P. J. Thompson, and G. A. Stewart House Dust Mite Allergens Induce Proinflammatory Cytokines from Respiratory Epithelial Cells: The Cysteine Protease Allergen, Der p 1, Activates Protease-Activated Receptor (PAR)-2 and Inactivates PAR-1 J. Immunol., October 15, 2002; 169(8): 4572 - 4578. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Vergnolle, C. K. Derian, M. R. D'Andrea, M. Steinhoff, and P. Andrade-Gordon Characterization of Thrombin-Induced Leukocyte Rolling and Adherence: A Potential Proinflammatory Role for Proteinase-Activated Receptor-4 J. Immunol., August 1, 2002; 169(3): 1467 - 1473. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Hollenberg and S. J. Compton International Union of Pharmacology. XXVIII. Proteinase-Activated Receptors Pharmacol. Rev., June 1, 2002; 54(2): 203 - 217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Asokananthan, P. T. Graham, J. Fink, D. A. Knight, A. J. Bakker, A. S. McWilliam, P. J. Thompson, and G. A. Stewart 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., April 1, 2002; 168(7): 3577 - 3585. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Al-Ani, M. Saifeddine, S. J. Wijesuriya, and M. D. Hollenberg Modified Proteinase-Activated Receptor-1 and -2 Derived Peptides Inhibit Proteinase-Activated Receptor-2 Activation by Trypsin J. Pharmacol. Exp. Ther., February 1, 2002; 300(2): 702 - 708. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. SCHMIDLIN, S. AMADESI, R. VIDIL, M. TREVISANI, N. MARTINET, G. CAUGHEY, M. TOGNETTO, G. CAVALLESCO, C. MAPP, P. GEPPETTI, et al. Expression and Function of Proteinase-activated Receptor 2 in Human Bronchial Smooth Muscle Am. J. Respir. Crit. Care Med., October 1, 2001; 164(7): 1276 - 1281. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Sun, M. A. Stacey, M. Schmidt, L. Mori, and S. Mattoli Interaction of Mite Allergens Der P3 and Der P9 with Protease-Activated Receptor-2 Expressed by Lung Epithelial Cells J. Immunol., July 15, 2001; 167(2): 1014 - 1021. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Macfarlane, M. J. Seatter, T. Kanke, G. D. Hunter, and R. Plevin Proteinase-Activated Receptors Pharmacol. Rev., June 1, 2001; 53(2): 245 - 282. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. D. Blackhart, L. Ruslim-Litrus, C.-C. Lu, V. L. Alves, W. Teng, R. M. Scarborough, E. E. Reynolds, and D. Oksenberg Extracellular Mutations of Protease-Activated Receptor-1 Result in Differential Activation by Thrombin and Thrombin Receptor Agonist Peptide Mol. Pharmacol., April 13, 2001; 58(6): 1178 - 1187. [Abstract] [Full Text]
|
|
|
|
 |
|
 F. Bono, P. Schaeffer, J.-P. Herault, C. Michaux, A.-L. Nestor, J.-C. Guillemot, and J.-M. Herbert Factor Xa Activates Endothelial Cells by a Receptor Cascade Between EPR-1 and PAR-2 Arterioscler. Thromb. Vasc. Biol., November 1, 2000; 20 (11): e107 - e112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. O'Brien, N. Prevost, M. Molino, M. K. Hollinger, M. J. Woolkalis, D. S. Woulfe, and L. F. Brass Thrombin Responses in Human Endothelial Cells. CONTRIBUTIONS FROM RECEPTORS OTHER THAN PAR1 INCLUDE THE TRANSACTIVATION OF PAR2 BY THROMBIN-CLEAVED PAR1 J. Biol. Chem., April 28, 2000; 275(18): 13502 - 13509. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-Q. Huang, J.-J. Li, and S. Karpatkin Thrombin Inhibits Tumor Cell Growth in Association with Up-regulation of p21waf/cip1 and Caspases via a p53-independent, STAT-1-dependent Pathway J. Biol. Chem., February 25, 2000; 275(9): 6462 - 6468. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C Chinni, M. de Niese, A. Jenkins, R. Pike, S. Bottomley, and E. Mackie Protease-activated receptor-2 mediates proliferative responses in skeletal myoblasts J. Cell Sci., January 12, 2000; 113(24): 4427 - 4433. [Abstract] [PDF]
|
|
|
|
 |
|
 I. A. Akers, M. Parsons, M. R. Hill, M. D. Hollenberg, S. Sanjar, G. J. Laurent, and R. J. McAnulty Mast cell tryptase stimulates human lung fibroblast proliferation via protease-activated receptor-2 Am J Physiol Lung Cell Mol Physiol, January 1, 2000; 278(1): L193 - L201. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Al-Ani, M. Saifeddine, A. Kawabata, B. Renaux, S. Mokashi, and M. D. Hollenberg Proteinase-Activated Receptor 2 (PAR2): Development of a Ligand-Binding Assay Correlating with Activation of PAR2 by PAR1- and PAR2-Derived Peptide Ligands J. Pharmacol. Exp. Ther., August 1, 1999; 290(2): 753 - 760. [Abstract] [Full Text]
|
|
|
|
|
|
B. P. Damiano, W.-M. Cheung, R. J. Santulli, W.-P. Fung-Leung, K. Ngo, R. D. Ye, A. L. Darrow, C. K. Derian, L. de Garavilla, and P. Andrade-Gordon 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., February 1, 1999; 288(2): 671 - 678. [Abstract] [Full Text]
|
|
|
|
|
|
A. Kawabata, M. Saifeddine, B. Al-Ani, L. Leblond, and M. D. Hollenberg Evaluation of Proteinase-Activated Receptor-1 (PAR1) Agonists and Antagonists Using a Cultured Cell Receptor Desensitization Assay: Activation of PAR2 by PAR1-Targeted Ligands J. Pharmacol. Exp. Ther., January 1, 1999; 288(1): 358 - 370. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. R. Hamilton, P. B. Nguyen, and T. M. Cocks Atypical Protease-Activated Receptor Mediates Endothelium-Dependent Relaxation of Human Coronary Arteries Circ. Res., June 29, 1998; 82(12): 1306 - 1311. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Vergnolle, W. K. Macnaughton, B. Al-Ani, M. Saifeddine, J. L. Wallace, and M. D. Hollenberg Proteinase-activated receptor 2 (PAR2)-activating peptides: Identification of a receptor distinct from PAR2 that regulates intestinal transport PNAS, June 23, 1998; 95(13): 7766 - 7771. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Dery, C. U. Corvera, M. Steinhoff, and N. W. Bunnett Proteinase-activated receptors: novel mechanisms of signaling by serine proteases Am J Physiol Cell Physiol, June 1, 1998; 274(6): C1429 - C1452. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Molino, P. N. Raghunath, A. Kuo, M. Ahuja, J. A. Hoxie, L. F. Brass, and E. S. Barnathan Differential Expression of Functional Protease-Activated Receptor-2 (PAR-2) in Human Vascular Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., May 1, 1998; 18(5): 825 - 832. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-L. Zheng, B. Renaux, and M. D. Hollenberg Parallel Contractile Signal Transduction Pathways Activated by Receptors for Thrombin and Epidermal Growth Factor-Urogastrone in Guinea Pig Gastric Smooth Muscle: Blockade by Inhibitors of Mitogen-Activated Protein Kinase-Kinase and Phosphatidyl Inositol 3'-Kinase J. Pharmacol. Exp. Ther., April 1, 1998; 285(1): 325 - 334. [Abstract] [Full Text]
|
|
|
|
|
|
H. Mirza, V. A. Schmidt, C. K. Derian, J. Jesty, and W. F. Bahou Mitogenic Responses Mediated Through the Proteinase-Activated Receptor-2 Are Induced by Expressed Forms of Mast Cell alpha - or beta -Tryptases Blood, November 15, 1997; 90(10): 3914 - 3922. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. E. Joyce, Y. Chen, R. A. Erger, G. A. Koretzky, and S. R. Lentz Functional Interactions Between the Thrombin Receptor and the T-Cell Antigen Receptor in Human T-Cell Lines Blood, September 1, 1997; 90(5): 1893 - 1901. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Kong, K. McConalogue, L. M. Khitin, M. D. Hollenberg, D. G. Payan, S. K. Bohm, and N. W. Bunnett Luminal trypsin may regulate enterocytes through proteinase-activated receptor 2 PNAS, August 5, 1997; 94(16): 8884 - 8889. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. M. Donovan, C. J. Pike, C. W. Cotman, and D. D. Cunningham Thrombin Induces Apoptosis in Cultured Neurons and Astrocytes via a Pathway Requiring Tyrosine Kinase and RhoA Activities J. Neurosci., July 15, 1997; 17(14): 5316 - 5326. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Molino, M. J. Woolkalis, J. Reavey-Cantwell, D. Pratico, P. Andrade-Gordon, E. S. Barnathan, and L. F. Brass Endothelial Cell Thrombin Receptors and PAR-2. TWO PROTEASE-ACTIVATED RECEPTORS LOCATED IN A SINGLE CELLULAR ENVIRONMENT J. Biol. Chem., April 25, 1997; 272(17): 11133 - 11141. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Renesto, M. Si-Tahar, M. Moniatte, V. Balloy, A. Van Dorsselaer, D. Pidard, and M. Chignard Specific Inhibition of Thrombin-Induced Cell Activation by the Neutrophil Proteinases Elastase, Cathepsin G, and Proteinase 3: Evidence for Distinct Cleavage Sites Within the Aminoterminal Domain of the Thrombin Receptor Blood, March 15, 1997; 89(6): 1944 - 1953. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Molino, E. S. Barnathan, R. Numerof, J. Clark, M. Dreyer, A. Cumashi, J. A. Hoxie, N. Schechter, M. Woolkalis, and L. F. Brass Interactions of Mast Cell Tryptase with Thrombin Receptors and PAR-2 J. Biol. Chem., February 14, 1997; 272(7): 4043 - 4049. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Howells, M. Macey, C Chinni, L Hou, M. Fox, P Harriott, and S. Stone Proteinase-activated receptor-2: expression by human neutrophils J. Cell Sci., January 4, 1997; 110(7): 881 - 887. [Abstract] [PDF]
|
|
|
|
|
|
S. J. Compton, J. A. Cairns, K.-J. Palmer, B. Al-Ani, M. D. Hollenberg, and A. F. Walls A Polymorphic Protease-activated Receptor 2 (PAR2) Displaying Reduced Sensitivity to Trypsin and Differential Responses to PAR Agonists J. Biol. Chem., December 8, 2000; 275(50): 39207 - 39212. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
