| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Department of Dermatology and Ludwig Boltzmann Institute for Cell and Immunobiology of the Skin (M.S., J.B., V.S., A.R., C.M., T.A.L.), University of Münster, 48149 Münster, Germany; and Department of Pharmacology (N.V., M.D.H.), University of Calgary, Calgary, Canada T2N 4N1
Correspondence: Address all correspondence and requests for reprints to: Martin Steinhoff, M.D., Ph.D., Department of Dermatology and Boltzmann Institute for Immunobiology of the Skin, University of Münster, von-Esmarch-Strasse 58, 48149 Münster, Germany. E-mail: msteinho{at}uni-muenster.de.
Serine proteinases such as thrombin, mast cell tryptase, trypsin, or cathepsin G, for example, are highly active mediators with diverse biological activities. So far, proteinases have been considered to act primarily as degradative enzymes in the extracellular space. However, their biological actions in tissues and cells suggest important roles as a part of the body’s hormonal communication system during inflammation and immune response. These effects can be attributed to the activation of a new subfamily of G protein-coupled receptors, termed proteinase-activated receptors (PARs). Four members of the PAR family have been cloned so far. Thus, certain proteinases act as signaling molecules that specifically regulate cells by activating PARs. After stimulation, PARs couple to various G proteins and activate signal transduction pathways resulting in the rapid transcription of genes that are involved in inflammation. For example, PARs are widely expressed by cells involved in immune responses and inflammation, regulate endothelial-leukocyte interactions, and modulate the secretion of inflammatory mediators or neuropeptides. Together, the PAR family necessitates a paradigm shift in thinking about hormone action, to include proteinases as key modulators of biological function. Novel compounds that can modulate PAR function may be potent candidates for the treatment of inflammatory or immune diseases.
This article has been cited by other articles:
 |
|
 |
|
  M. D. Hollenberg, B. Renaux, E. Hyun, S. Houle, N. Vergnolle, M. Saifeddine, and R. Ramachandran Derivatized 2-Furoyl-LIGRLO-amide, a Versatile and Selective Probe for Proteinase-Activated Receptor 2: Binding and Visualization J. Pharmacol. Exp. Ther., August 1, 2008; 326(2): 453 - 462. [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]
|
|
|
|
 |
|
 M. Feld, V. M. Shpacovitch, C. Ehrhardt, C. Kerkhoff, M. D. Hollenberg, N. Vergnolle, S. Ludwig, and M. Steinhoff Agonists of Proteinase-Activated Receptor-2 Enhance IFN-{gamma}-Inducible Effects on Human Monocytes: Role in Influenza A Infection J. Immunol., May 15, 2008; 180(10): 6903 - 6910. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Q. van der Merwe, M. D. Hollenberg, and W. K. MacNaughton EGF receptor transactivation and MAP kinase mediate proteinase-activated receptor-2-induced chloride secretion in intestinal epithelial cells Am J Physiol Gastrointest Liver Physiol, February 1, 2008; 294(2): G441 - G451. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. Moraes, R. Martin, J. D. Plumb, E. Vachon, C. M. Cameron, A. Danesh, D. J. Kelvin, W. Ruf, and G. P. Downey Role of PAR2 in murine pulmonary pseudomonal infection Am J Physiol Lung Cell Mol Physiol, February 1, 2008; 294(2): L368 - L377. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Alier, J. A. Endicott, P. L. Stemkowski, N. Cenac, L. Cellars, K. Chapman, P. Andrade-Gordon, N. Vergnolle, and P. A. Smith Intrathecal Administration of Proteinase-Activated Receptor-2 Agonists Produces Hyperalgesia by Exciting the Cell Bodies of Primary Sensory Neurons J. Pharmacol. Exp. Ther., January 1, 2008; 324(1): 224 - 233. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Saifeddine, M. L. Seymour, Y.-P. Xiao, S. J. Compton, S. Houle, R. Ramachandran, W. K. MacNaughton, S. Simonet, C. Vayssettes-Courchay, T. J. Verbeuren, et al. Proteinase-activated receptor-2 activating peptides: distinct canine coronary artery receptor systems Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3279 - H3289. [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]
|
|
|
|
 |
|
 W. Luo, Y. Wang, and G. Reiser p24A, a Type I Transmembrane Protein, Controls ARF1-dependent Resensitization of Protease-activated Receptor-2 by Influence on Receptor Trafficking J. Biol. Chem., October 12, 2007; 282(41): 30246 - 30255. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. I. Jiang, J. Collins, R. Davis, K.-M. Lin, D. DeCamp, T. Roach, R. Hsueh, R. A. Rebres, E. M. Ross, R. Taussig, et al. Use of a cAMP BRET Sensor to Characterize a Novel Regulation of cAMP by the Sphingosine 1-Phosphate/G13 Pathway J. Biol. Chem., April 6, 2007; 282(14): 10576 - 10584. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. D'hondt, S. P. Srinivas, J. Vereecke, and B. Himpens Adenosine Opposes Thrombin-Induced Inhibition of Intercellular Calcium Wave in Corneal Endothelial Cells Invest. Ophthalmol. Vis. Sci., April 1, 2007; 48(4): 1518 - 1527. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Salah, M. Maoz, E. Pokroy, M. Lotem, R. Bar-Shavit, and B. Uziely Protease-Activated Receptor-1 (hPar1), A Survival Factor Eliciting Tumor Progression Mol. Cancer Res., March 1, 2007; 5(3): 229 - 240. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Holinstat, B. Voss, M. L. Bilodeau, and H. E. Hamm Protease-Activated Receptors Differentially Regulate Human Platelet Activation through a Phosphatidic Acid-Dependent Pathway Mol. Pharmacol., March 1, 2007; 71(3): 686 - 694. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Ramachandran, L. R. Sadofsky, Y. Xiao, A. Botham, M. Cowen, A. H. Morice, and S. J Compton Inflammatory mediators modulate thrombin and cathepsin-G signaling in human bronchial fibroblasts by inducing expression of proteinase-activated receptor-4 Am J Physiol Lung Cell Mol Physiol, March 1, 2007; 292(3): L788 - L798. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Ayala, D. J. Warejcka, M. Olague-Marchan, and S. S. Twining Corneal Activation of Prothrombin to Form Thrombin, Independent of Vascular Injury Invest. Ophthalmol. Vis. Sci., January 1, 2007; 48(1): 134 - 143. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. F. MERCER, X. DENG, and R. C. CHAMBERS Signaling Pathways Involved in Proteinase-Activated Receptor1-Induced Proinflammatory and Profibrotic Mediator Release Following Lung Injury Ann. N.Y. Acad. Sci., January 1, 2007; 1096(1): 86 - 88. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Oikonomopoulou, K. K. Hansen, M. Saifeddine, I. Tea, M. Blaber, S. I. Blaber, I. Scarisbrick, P. Andrade-Gordon, G. S. Cottrell, N. W. Bunnett, et al. Proteinase-activated Receptors, Targets for Kallikrein Signaling J. Biol. Chem., October 27, 2006; 281(43): 32095 - 32112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Roosterman, T. Goerge, S. W. Schneider, N. W. Bunnett, and M. Steinhoff Neuronal control of skin function: the skin as a neuroimmunoendocrine organ. Physiol Rev, October 1, 2006; 86(4): 1309 - 1379. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-H. Lin, H.-W. Cheng, M.-J. Hsu, M.-C. Chen, C.-C. Lin, and B.-C. Chen c-Src Mediates Thrombin-Induced NF-{kappa}B Activation and IL-8/CXCL8 Expression in Lung Epithelial Cells. J. Immunol., September 1, 2006; 177(5): 3427 - 3438. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Goerge, A. Barg, E.-M. Schnaeker, B. Poppelmann, V. Shpacovitch, A. Rattenholl, C. Maaser, T. A. Luger, M. Steinhoff, and S. W. Schneider Tumor-derived matrix metalloproteinase-1 targets endothelial proteinase-activated receptor 1 promoting endothelial cell activation. Cancer Res., August 1, 2006; 66(15): 7766 - 7774. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Ramachandran, A. H. Morice, and S. J. Compton Proteinase-Activated Receptor2 Agonists Upregulate Granulocyte Colony-Stimulating Factor, IL-8, and VCAM-1 Expression in Human Bronchial Fibroblasts Am. J. Respir. Cell Mol. Biol., July 1, 2006; 35(1): 133 - 141. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Riteau, C. de Vaureix, and F. Lefevre Trypsin increases pseudorabies virus production through activation of the ERK signalling pathway. J. Gen. Virol., May 1, 2006; 87(Pt 5): 1109 - 1112. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Noorbakhsh, S. Tsutsui, N. Vergnolle, L. A. Boven, N. Shariat, M. Vodjgani, K. G. Warren, P. Andrade-Gordon, M. D. Hollenberg, and C. Power Proteinase-activated receptor 2 modulates neuroinflammation in experimental autoimmune encephalomyelitis and multiple sclerosis J. Exp. Med., February 21, 2006; 203(2): 425 - 435. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Ford, D. B. Guiliano, Y. Oksov, A. K. Debnath, J. Liu, S. A. Williams, M. L. Blaxter, and S. Lustigman Characterization of a Novel Filarial Serine Protease Inhibitor, Ov-SPI-1, from Onchocerca volvulus, with Potential Multifunctional Roles during Development of the Parasite J. Biol. Chem., December 9, 2005; 280(49): 40845 - 40856. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Inoue, Y. Matsuwaki, S.-H. Shin, J. U. Ponikau, and H. Kita Nonpathogenic, Environmental Fungi Induce Activation and Degranulation of Human Eosinophils J. Immunol., October 15, 2005; 175(8): 5439 - 5447. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
