Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

Pair your accounts.

Export articles to Mendeley

Get article recommendations from ACS based on references in your Mendeley library.

You’ve supercharged your research process with ACS and Mendeley!

STEP 1:
Click to create an ACS ID

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

Please note: If you switch to a different device, you may be asked to login again with only your ACS ID.

MENDELEY PAIRING EXPIRED
Your Mendeley pairing has expired. Please reconnect
ACS Publications. Most Trusted. Most Cited. Most Read
Proteolysis of the Exodomain of Recombinant Protease-Activated Receptors:  Prediction of Receptor Activation or Inactivation by MALDI Mass Spectrometry

OR SEARCH CITATIONS

My Activity
Publications

Figure 1Loading Img
Download Hi-Res ImageDownload to MS-PowerPointCite This:Biochemistry 2000, 39, 35, 10812-10822
    Article

    Proteolysis of the Exodomain of Recombinant Protease-Activated Receptors:  Prediction of Receptor Activation or Inactivation by MALDI Mass Spectrometry†
    Click to copy article linkArticle link copied!

    View Author Information
    Laboratoire de Spectrométrie de Masse Bio Organique, Université Louis Pasteur, Strasbourg, France, INSERM U311, Etablissement Français du Sang-Alsace, Strasbourg, France, and Dipartimento di Biochimica e Biotecnologie Mediche, Universita “Federico II”, Naples, Italy
    Other Access Options

    Biochemistry

    Cite this: Biochemistry 2000, 39, 35, 10812–10822
    Click to copy citationCitation copied!
    https://doi.org/10.1021/bi0003341
    Published August 10, 2000
    Copyright © 2000 American Chemical Society
    Request reuse permissions

    Abstract

    Click to copy section linkSection link copied!

    Protease-activated receptors (PARs) mediate cell activation after proteolytic cleavage of their extracellular amino terminus. Thrombin selectively cleaves PAR1, PAR3, and PAR4 to induce activation of platelets and vascular cells, while PAR2 is preferentially cleaved by trypsin. In pathological situations, other proteolytic enzymes may be generated in the circulation and could modify the responses of PARs by cleaving their extracellular domains. To assess the ability of such proteases to activate or inactivate PARs, we designed a strategy for locating cleavage sites on the exofacial NH2-terminal fragments of the receptors. The first extracellular segments of PAR1 (PAR1E) and PAR2 (PAR2E) expressed as recombinant proteins in Escherichia coli were incubated with a series of proteases likely to be encountered in the circulation during thrombosis or inflammation. Kinetic and dose−response studies were performed, and the cleavage products were analyzed by MALDI-TOF mass spectrometry. Thrombin cleaved PAR1E at the Arg41−Ser42 activation site at concentrations known to induce cellular activation, supporting a native conformation of the recombinant polypeptide. Plasmin, calpain and leukocyte elastase, cathepsin G, and proteinase 3 cleaved at multiple sites and would be expected to disable PAR1 by cleaving COOH-terminal to the activation site. Cleavage specificities were further confirmed using activation site defective PAR1E S42P mutant polypeptides. Surface plasmon resonance studies on immobilized PAR1E or PAR1E S42P were consistent with cleavage results obtained in solution and allowed us to determine affinities of PAR1E−thrombin binding. FACS analyses of intact platelets confirmed the cleavage of PAR1 downstream of the Arg41−Ser42 site. Mass spectrometry studies of PAR2E predicted activation of PAR2 by trypsin through cleavage at the Arg36−Ser37 site, no effect of thrombin, and inactivation of the receptor by plasmin, calpain and leukocyte elastase, cathepsin G, and proteinase 3. The inhibitory effect of elastase was confirmed on native PAR1 and PAR2 on the basis of Ca2+ signaling studies in endothelial cells. It was concluded that none of the main proteases generated during fibrinolysis or inflammation appears to be able to signal through PAR1 or PAR2. This strategy provides results which can be extended to the native receptor to predict its activation or inactivation, and it could likewise be used to study other PARs or protease-dependent processes.

    Copyright © 2000 American Chemical Society

    Subjects

    what are subjects

    Read this article

    To access this article, please review the available access options below.

    Get instant access

    Purchase Access

    Read this article for 48 hours. Check out below using your ACS ID or as a guest.

    Recommended

    Access through Your Institution

    You may have access to this article through your institution.

    Your institution does not have access to this content. Add or change your institution or let them know you’d like them to include access.

    †

     The Conseil Régional d'Alsace is acknowledged for a financial support in the acquisition of a Biflex II Bruker MALDI-TOF mass spectrometer.

    ‡

     Université Louis Pasteur.

    §

     Etablissement Français du Sang-Alsace.

    ‖

     Universita “Federico II”.

    *

     To whom correspondence should be addressed:  INSERM U.311, Etablissement Français du Sang-Alsace, 10 rue Spielmann, BP 36, 67065 Strasbourg Cédex, France. Telephone:  +33-388-21-25-25. Fax:  +33-388-21-25-21. E-mail:  [email protected].

    Cited By

    Click to copy section linkSection link copied!

    This article is cited by 77 publications.

    1. Gal Reches, Ron Piran. Par2-mediated responses in inflammation and regeneration: choosing between repair and damage. Inflammation and Regeneration 2024, 44 (1) https://doi.org/10.1186/s41232-024-00338-1
    2. Chloe J. Peach, Laura E. Edgington-Mitchell, Nigel W. Bunnett, Brian L. Schmidt. Protease-activated receptors in health and disease. Physiological Reviews 2023, 103 (1) , 717-785. https://doi.org/10.1152/physrev.00044.2021
    3. Saravanan Subramaniam, Wolfram Ruf, Markus Bosmann. Advocacy of targeting protease‐activated receptors in severe coronavirus disease 2019. British Journal of Pharmacology 2022, 179 (10) , 2086-2099. https://doi.org/10.1111/bph.15587
    4. Mitali Das, Sujay Subbayya Ithychanda, Edward F. Plow. Histone 2B Facilitates Plasminogen-Enhanced Endothelial Migration through Protease-Activated Receptor 1 (PAR1) and Protease-Activated Receptor 2 (PAR2). Biomolecules 2022, 12 (2) , 211. https://doi.org/10.3390/biom12020211
    5. Michelle De bruyn, Hannah Ceuleers, Nikita Hanning, Maya Berg, Joris G. De Man, Paco Hulpiau, Cedric Hermans, Ulf-Håkan Stenman, Hannu Koistinen, Anne-Marie Lambeir, Benedicte Y. De Winter, Ingrid De Meester. Proteolytic Cleavage of Bioactive Peptides and Protease-Activated Receptors in Acute and Post-Colitis. International Journal of Molecular Sciences 2021, 22 (19) , 10711. https://doi.org/10.3390/ijms221910711
    6. Márta L. Debreczeni, Zsuzsanna Németh, Erika Kajdácsi, Henriette Farkas, László Cervenak. Molecular Dambusters: What Is Behind Hyperpermeability in Bradykinin-Mediated Angioedema?. Clinical Reviews in Allergy & Immunology 2021, 60 (3) , 318-347. https://doi.org/10.1007/s12016-021-08851-8
    7. Arundhasa Chandrabalan, Rithwik Ramachandran. Molecular mechanisms regulating Proteinase‐Activated Receptors (PARs). The FEBS Journal 2021, 288 (8) , 2697-2726. https://doi.org/10.1111/febs.15829
    8. Efrat Shavit-Stein, Ekaterina Mindel, Shany Guly Gofrit, Joab Chapman, Nicola Maggio, . Ischemic stroke in PAR1 KO mice: Decreased brain plasmin and thrombin activity along with decreased infarct volume. PLOS ONE 2021, 16 (3) , e0248431. https://doi.org/10.1371/journal.pone.0248431
    9. Abishek Iyer, Tyrone L. R. Humphries, Evan P. Owens, Kong-Nan Zhao, Paul P. Masci, David W. Johnson, David Nikolic-Paterson, Glenda C. Gobe, David P. Fairlie, David A. Vesey. PAR2 Activation on Human Kidney Tubular Epithelial Cells Induces Tissue Factor Synthesis, That Enhances Blood Clotting. Frontiers in Physiology 2021, 12 https://doi.org/10.3389/fphys.2021.615428
    10. Karla A. Oliveira, Ricardo J. S. Torquato, Daniela C. G. Garcia Lustosa, Tales Ribeiro, Bruno W. L. Nascimento, Lilian C. G. de Oliveira, Maria A. Juliano, Thaysa Paschoalin, Virginia S. Lemos, Ricardo N. Araujo, Marcos H. Pereira, Aparecida S. Tanaka. Proteolytic activity of Triatoma infestans saliva associated with PAR-2 activation and vasodilation. Journal of Venomous Animals and Toxins including Tropical Diseases 2021, 27 https://doi.org/10.1590/1678-9199-jvatitd-2020-0098
    11. Jason J McDougall, Miranda McConnell, Allison R Reid. Intracellular versus extracellular inhibition of calpain I causes differential effects on pain in a rat model of joint inflammation. Molecular Pain 2021, 17 https://doi.org/10.1177/17448069211016141
    12. Dorothea M. Heuberger, Reto A. Schuepbach. Protease-activated receptors (PARs): mechanisms of action and potential therapeutic modulators in PAR-driven inflammatory diseases. Thrombosis Journal 2019, 17 (1) https://doi.org/10.1186/s12959-019-0194-8
    13. Morgane Sébert, Nuria Sola-Tapias, Emmanuel Mas, Frédérick Barreau, Audrey Ferrand. Protease-Activated Receptors in the Intestine: Focus on Inflammation and Cancer. Frontiers in Endocrinology 2019, 10 https://doi.org/10.3389/fendo.2019.00717
    14. Dorothea M. Heuberger, Alessandro G. Franchini, Jerzy Madon, Reto A. Schuepbach. Thrombin cleaves and activates the protease-activated receptor 2 dependent on thrombomodulin co-receptor availability. Thrombosis Research 2019, 177 , 91-101. https://doi.org/10.1016/j.thromres.2019.02.032
    15. Jessica L. Sessenwein, Corey C. Baker, Sabindra Pradhananga, Megan E. Maitland, Elaine O. Petrof, Emma Allen-Vercoe, Curtis Noordhof, David E. Reed, Stephen J. Vanner, Alan E. Lomax. Protease-Mediated Suppression of DRG Neuron Excitability by Commensal Bacteria. The Journal of Neuroscience 2017, 37 (48) , 11758-11768. https://doi.org/10.1523/JNEUROSCI.1672-17.2017
    16. Nathan J. White, Kevin R. Ward, Shibani Pati, Geir Strandenes, Andrew P. Cap. Hemorrhagic blood failure. Journal of Trauma and Acute Care Surgery 2017, 82 (6S) , S41-S49. https://doi.org/10.1097/TA.0000000000001436
    17. Roland Böttger, Daniel Knappe, Ralf Hoffmann. Readily adaptable release kinetics of prodrugs using protease-dependent reversible PEGylation. Journal of Controlled Release 2016, 230 , 88-94. https://doi.org/10.1016/j.jconrel.2016.04.010
    18. Peishen Zhao, TinaMarie Lieu, Nicholas Barlow, Silvia Sostegni, Silke Haerteis, Christoph Korbmacher, Wolfgang Liedtke, Nestor N. Jimenez-Vargas, Stephen J. Vanner, Nigel W. Bunnett. Neutrophil Elastase Activates Protease-activated Receptor-2 (PAR2) and Transient Receptor Potential Vanilloid 4 (TRPV4) to Cause Inflammation and Pain. Journal of Biological Chemistry 2015, 290 (22) , 13875-13887. https://doi.org/10.1074/jbc.M115.642736
    19. Miriam Ender, Federica Andreoni, Annelies Sophie Zinkernagel, Reto Andreas Schuepbach, . Streptococcal SpeB Cleaved PAR-1 Suppresses ERK Phosphorylation and Blunts Thrombin-Induced Platelet Aggregation. PLoS ONE 2013, 8 (11) , e81298. https://doi.org/10.1371/journal.pone.0081298
    20. Christian Lévêque, Géraldine Ferracci, Yves Maulet, Chloé Grand-Masson, Marie-Pierre Blanchard, Michael Seagar, Oussama El Far. A substrate sensor chip to assay the enzymatic activity of Botulinum neurotoxin A. Biosensors and Bioelectronics 2013, 49 , 276-281. https://doi.org/10.1016/j.bios.2013.05.032
    21. Christine Gaboriaud, Rajesh Kumar Gupta, Lydie Martin, Monique Lacroix, Laurence Serre, Florence Teillet, Gérard J. Arlaud, Véronique Rossi, Nicole M. Thielens, . The Serine Protease Domain of MASP-3: Enzymatic Properties and Crystal Structure in Complex with Ecotin. PLoS ONE 2013, 8 (7) , e67962. https://doi.org/10.1371/journal.pone.0067962
    22. Kaustav Chakraborty, Arindam Bhattacharyya. Role of Proteases in Inflammatory Lung Diseases. 2013, 361-385. https://doi.org/10.1007/978-1-4614-9233-7_21
    23. Elena I. Deryugina, James P. Quigley. Cell Surface Remodeling by Plasmin: A New Function for an Old Enzyme. Journal of Biomedicine and Biotechnology 2012, 2012 , 1-21. https://doi.org/10.1155/2012/564259
    24. Yu Pei Xiao, Alyn H. Morice, Steven J. Compton, Laura Sadofsky. N-Linked Glycosylation Regulates Human Proteinase-activated Receptor-1 Cell Surface Expression and Disarming via Neutrophil Proteinases and Thermolysin. Journal of Biological Chemistry 2011, 286 (26) , 22991-23002. https://doi.org/10.1074/jbc.M110.204271
    25. Rithwik Ramachandran, Koichiro Mihara, Hyunjae Chung, Bernard Renaux, Chang S. Lau, Daniel A. Muruve, Kathryn A. DeFea, Michel Bouvier, Morley D. Hollenberg. Neutrophil Elastase Acts as a Biased Agonist for Proteinase-activated Receptor-2 (PAR2). Journal of Biological Chemistry 2011, 286 (28) , 24638-24648. https://doi.org/10.1074/jbc.M110.201988
    26. Mark N. Adams, Rithwik Ramachandran, Mei-Kwan Yau, Jacky Y. Suen, David P. Fairlie, Morley D. Hollenberg, John D. Hooper. Structure, function and pathophysiology of protease activated receptors. Pharmacology & Therapeutics 2011, 130 (3) , 248-282. https://doi.org/10.1016/j.pharmthera.2011.01.003
    27. Kai-Li He, Guangzhi Sui, Huabao Xiong, M. Johan Broekman, Bihui Huang, Aaron J. Marcus, Katherine A. Hajjar. Feedback Regulation of Endothelial Cell Surface Plasmin Generation by PKC-dependent Phosphorylation of Annexin A2. Journal of Biological Chemistry 2011, 286 (17) , 15428-15439. https://doi.org/10.1074/jbc.M110.185058
    28. Bénédicte Manoury, Ali Roghanian, Jean-Michel Sallenave. Serine and Cysteine Proteases and Their Inhibitors as Antimicrobial Agents and Immune Modulators. 2011, 27-50. https://doi.org/10.1007/978-3-0348-0157-7_2
    29. Terence Peters, Peter J Henry. Protease‐activated receptors and prostaglandins in inflammatory lung disease. British Journal of Pharmacology 2009, 158 (4) , 1017-1033. https://doi.org/10.1111/j.1476-5381.2009.00449.x
    30. Hongjie Yuan, Katie M. Vance, Candice E. Junge, Matthew T. Geballe, James P. Snyder, John R. Hepler, Manuel Yepes, Chian-Ming Low, Stephen F. Traynelis. The Serine Protease Plasmin Cleaves the Amino-terminal Domain of the NR2A Subunit to Relieve Zinc Inhibition of the N-Methyl-d-aspartate Receptors. Journal of Biological Chemistry 2009, 284 (19) , 12862-12873. https://doi.org/10.1074/jbc.M805123200
    31. Kirsten L. Elzer, Deborah A. Heitzman, Mitchell I. Chernin, Josef F. Novak. Differential Effects of Serine Proteases on the Migration of Normal and Tumor Cells: Implications for Tumor Microenvironment. Integrative Cancer Therapies 2008, 7 (4) , 282-294. https://doi.org/10.1177/1534735408327250
    32. Guido Mannaioni, Anna G. Orr, Cecily E. Hamill, Hongjie Yuan, Katherine H. Pedone, Kelly L. McCoy, Rolando Berlinguer Palmini, Candice E. Junge, C. Justin Lee, Manuel Yepes, John R. Hepler, Stephen F. Traynelis. Plasmin Potentiates Synaptic N-Methyl-D-aspartate Receptor Function in Hippocampal Neurons through Activation of Protease-activated Receptor-1. Journal of Biological Chemistry 2008, 283 (29) , 20600-20611. https://doi.org/10.1074/jbc.M803015200
    33. Gary Franklin, Alan McWhirter. Real‐time Characterization of B iomolecular Interactions using Biacore's Optical Biosensors. 2008, 57-106. https://doi.org/10.1002/9783527610754.fa06
    34. Ali Roghanian, Jean-Michel Sallenave. Neutrophil Elastase (NE) and NE Inhibitors: Canonical and Noncanonical Functions in Lung Chronic Inflammatory Diseases (Cystic Fibrosis and Chronic Obstructive Pulmonary Disease). Journal of Aerosol Medicine and Pulmonary Drug Delivery 2008, 21 (1) , 125-144. https://doi.org/10.1089/jamp.2007.0653
    35. Ali Roghanian, Jean-Michel Sallenave. Neutrophil Elastase (NE) and NE Inhibitors: Canonical and Noncanonical Functions in Lung Chronic Inflammatory Diseases (Cystic Fibrosis and Chronic Obstructive Pulmonary Disease). Journal of Aerosol Medicine 2008, Article ASAP.
    36. Taku Nagai, Toshitaka Nabeshima, Kiyofumi Yamada. Basic and Translational Research on Proteinase-Activated Receptors: Regulation of Nicotine Reward by the Tissue Plasminogen Activator (tPA) – Plasmin System via Proteinase-Activated Receptor 1. Journal of Pharmacological Sciences 2008, 108 (4) , 408-414. https://doi.org/10.1254/jphs.08R04FM
    37. V. Shpacovitch, M. Feld, N.W. Bunnett, M. Steinhoff. Protease-activated receptors: novel PARtners in innate immunity. Trends in Immunology 2007, 28 (12) , 541-550. https://doi.org/10.1016/j.it.2007.09.001
    38. Charles E. Reed. Inflammatory effect of environmental proteases on airway mucosa. Current Allergy and Asthma Reports 2007, 7 (5) , 368-374. https://doi.org/10.1007/s11882-007-0056-5
    39. Wolfgang Knecht, Graeme S. Cottrell, Silvia Amadesi, Johanna Mohlin, Anita Skåregärde, Karin Gedda, Anders Peterson, Kevin Chapman, Morley D. Hollenberg, Nathalie Vergnolle, Nigel W. Bunnett. Trypsin IV or Mesotrypsin and p23 Cleave Protease-activated Receptors 1 and 2 to Induce Inflammation and Hyperalgesia. Journal of Biological Chemistry 2007, 282 (36) , 26089-26100. https://doi.org/10.1074/jbc.M703840200
    40. Antonella Nesi, Marco Fragai. Substrate Specificities of Matrix Metalloproteinase 1 in PAR‐1 Exodomain Proteolysis. ChemBioChem 2007, 8 (12) , 1367-1369. https://doi.org/10.1002/cbic.200700055
    41. Elena Sokolova, Georg Reiser. A novel therapeutic target in various lung diseases: Airway proteases and protease-activated receptors. Pharmacology & Therapeutics 2007, 115 (1) , 70-83. https://doi.org/10.1016/j.pharmthera.2007.04.002
    42. Tetsuhiro Fujiyoshi, Katsuya Hirano, Mayumi Hirano, Junji Nishimura, Shosuke Takahashi, Hideo Kanaide. Plasmin Induces Endothelium-Dependent Nitric Oxide–Mediated Relaxation in the Porcine Coronary Artery. Arteriosclerosis, Thrombosis, and Vascular Biology 2007, 27 (4) , 949-954. https://doi.org/10.1161/01.ATV.0000259360.33203.00
    43. Steeve Houle, Morley D. Hollenberg. Proteinase-Activated Receptors. 2007, 1-12. https://doi.org/10.1016/B978-008055232-3.60338-1
    44. Katsuya Hirano. The Roles of Proteinase-Activated Receptors in the Vascular Physiology and Pathophysiology. Arteriosclerosis, Thrombosis, and Vascular Biology 2007, 27 (1) , 27-36. https://doi.org/10.1161/01.ATV.0000251995.73307.2d
    45. Taku Nagai, Mina Ito, Noritaka Nakamichi, Hiroyuki Mizoguchi, Hiroyuki Kamei, Ayumi Fukakusa, Toshitaka Nabeshima, Kazuhiro Takuma, Kiyofumi Yamada. The Rewards of Nicotine: Regulation by Tissue Plasminogen Activator–Plasmin System through Protease Activated Receptor-1. The Journal of Neuroscience 2006, 26 (47) , 12374-12383. https://doi.org/10.1523/JNEUROSCI.3139-06.2006
    46. Christine T. N. Pham. Neutrophil serine proteases: specific regulators of inflammation. Nature Reviews Immunology 2006, 6 (7) , 541-550. https://doi.org/10.1038/nri1841
    47. Elena Csernok, MaiXing Ai, Wolfgang L. Gross, Daniel Wicklein, Arnd Petersen, Buko Lindner, Peter Lamprecht, Julia U. Holle, Bernhard Hellmich. Wegener autoantigen induces maturation of dendritic cells and licenses them for Th1 priming via the protease-activated receptor-2 pathway. Blood 2006, 107 (11) , 4440-4448. https://doi.org/10.1182/blood-2005-05-1875
    48. Yong-Jun Yin, Vered Katz, Zaidoun Salah, Myriam Maoz, Irit Cohen, Beatrice Uziely, Hagit Turm, Sorina Grisaru-Granovsky, Hiromu Suzuki, Rachel Bar-Shavit. Mammary Gland Tissue Targeted Overexpression of Human Protease-Activated Receptor 1 Reveals a Novel Link to β-Catenin Stabilization. Cancer Research 2006, 66 (10) , 5224-5233. https://doi.org/10.1158/0008-5472.CAN-05-4234
    49. Yves Laumonnier, Tatiana Syrovets, Ladislav Burysek, Thomas Simmet. Identification of the annexin A2 heterotetramer as a receptor for the plasmin-induced signaling in human peripheral monocytes. Blood 2006, 107 (8) , 3342-3349. https://doi.org/10.1182/blood-2005-07-2840
    50. Michel Chignard, Dominique Pidard. Neutrophil and Pathogen Proteinases versus Proteinase-Activated Receptor-2 Lung Epithelial Cells. American Journal of Respiratory Cell and Molecular Biology 2006, 34 (4) , 394-398. https://doi.org/10.1165/rcmb.2005-0250TR
    51. Jon R. Ward, Steven K. Dower, Moira K.B. Whyte, David J. Buttle, Ian Sabroe. Potentiation of TLR4 signalling by plasmin activity. Biochemical and Biophysical Research Communications 2006, 341 (2) , 299-303. https://doi.org/10.1016/j.bbrc.2005.12.188
    52. Shunji Sugawara. Interleukin-18 and oral mucosal immunity. International Congress Series 2005, 1284 , 113-122. https://doi.org/10.1016/j.ics.2005.06.004
    53. Sophie Dulon, Dominique Leduc, Graeme S. Cottrell, Jacques D'Alayer, Kristina K. Hansen, Nigel W. Bunnett, Morley D. Hollenberg, Dominique Pidard, Michel Chignard. Pseudomonas aeruginosa Elastase Disables Proteinase-Activated Receptor 2 in Respiratory Epithelial Cells. American Journal of Respiratory Cell and Molecular Biology 2005, 32 (5) , 411-419. https://doi.org/10.1165/rcmb.2004-0274OC
    54. O. WIEDOW, U. MEYER‐HOFFERT. Neutrophil serine proteases: potential key regulators of cell signalling during inflammation. Journal of Internal Medicine 2005, 257 (4) , 319-328. https://doi.org/10.1111/j.1365-2796.2005.01476.x
    55. S.K. MANDAL, L.V.M. RAO, T.T.T. TRAN, U.R. PENDURTHI. A novel mechanism of plasmin-induced mitogenesis in fibroblasts. Journal of Thrombosis and Haemostasis 2005, 3 (1) , 163-169. https://doi.org/10.1111/j.1538-7836.2004.01054.x
    56. Ulf Meyer-Hoffert, Jana Wingertszahn, Oliver Wiedow. Human Leukocyte Elastase Induces Keratinocyte Proliferation by Epidermal Growth Factor Receptor Activation. Journal of Investigative Dermatology 2004, 123 (2) , 338-345. https://doi.org/10.1111/j.0022-202X.2004.23202.x
    57. Tetsuzo Nakayama, Katsuya Hirano, Mayumi Hirano, Junji Nishimura, Hirotaka Kuga, Katsuya Nakamura, Shosuke Takahashi, Hideo Kanaide. Inactivation of protease-activated receptor-1 by proteolytic removal of the ligand region in vascular endothelial cells. Biochemical Pharmacology 2004, 68 (1) , 23-32. https://doi.org/10.1016/j.bcp.2004.03.005
    58. Tim Tralau, Ulf Meyer‐Hoffert, Jens‐M. Schröder, Oliver Wiedow. Human leukocyte elastase and cathepsin G are specific inhibitors of C5a‐dependent neutrophil enzyme release and chemotaxis. Experimental Dermatology 2004, 13 (5) , 316-325. https://doi.org/10.1111/j.0906-6705.2004.00145.x
    59. Ulf Meyer‐Hoffert, Christina Rogalski, Stefanie Seifert, Gero Schmeling, Jana Wingertszahn, Ehrhardt Proksch, Oliver Wiedow. Trypsin induces epidermal proliferation and inflammation in murine skin. Experimental Dermatology 2004, 13 (4) , 234-241. https://doi.org/10.1111/j.0906-6705.2004.00159.x
    60. Akiko Uehara, Koji Muramoto, Haruhiko Takada, Shunji Sugawara. Neutrophil Serine Proteinases Activate Human Nonepithelial Cells to Produce Inflammatory Cytokines Through Protease-Activated Receptor 2. The Journal of Immunology 2003, 170 (11) , 5690-5696. https://doi.org/10.4049/jimmunol.170.11.5690
    61. Bahjat Al-Ani, Morley D. Hollenberg. Selective Tryptic Cleavage at the Tethered Ligand Site of the Amino Terminal Domain of Proteinase-Activated Receptor-2 in Intact Cells. Journal of Pharmacology and Experimental Therapeutics 2003, 304 (3) , 1120-1128. https://doi.org/10.1124/jpet.102.043844
    62. Sophie Dulon, Céline Candé, Nigel W. Bunnett, Morley D. Hollenberg, Michel Chignard, Dominique Pidard. Proteinase-Activated Receptor-2 and Human Lung Epithelial Cells. American Journal of Respiratory Cell and Molecular Biology 2003, 28 (3) , 339-346. https://doi.org/10.1165/rcmb.4908
    63. Laurent Baud, Bruno Fouqueray, Agnès Bellocq, Julie Peltier. Les calpaïnes participent au développement de la réaction inflammatoire. médecine/sciences 2003, 19 (1) , 71-76. https://doi.org/10.1051/medsci/200319171
    64. Katsuya Hirano, Hideo Kanaide. Role of Protease-activated Receptors in the Vascular System. Journal of Atherosclerosis and Thrombosis 2003, 10 (4) , 211-225. https://doi.org/10.5551/jat.10.211
    65. Tetsuzo Nakayama, Katsuya Hirano, Yoshinobu Shintani, Junji Nishimura, Akio Nakatsuka, Hirotaka Kuga, Shosuke Takahashi, Hideo Kanaide. Unproductive cleavage and the inactivation of protease‐activated receptor‐1 by trypsin in vascular endothelial cells. British Journal of Pharmacology 2003, 138 (1) , 121-130. https://doi.org/10.1038/sj.bjp.0705008
    66. Nithiananthan Asokananthan, Peter T. Graham, David J. Stewart, Anthony J. Bakker, Karin A. Eidne, Philip J. Thompson, Geoffrey 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. The Journal of Immunology 2002, 169 (8) , 4572-4578. https://doi.org/10.4049/jimmunol.169.8.4572
    67. Rommel S. Lan, Geoffrey A. Stewart, Peter J. Henry. Role of protease-activated receptors in airway function: a target for therapeutic intervention?. Pharmacology & Therapeutics 2002, 95 (3) , 239-257. https://doi.org/10.1016/S0163-7258(02)00237-1
    68. Usha R. Pendurthi, Mylinh Ngyuen, Patricia Andrade-Gordon, Lars C. Petersen, L. Vijaya Mohan Rao. Plasmin Induces Cyr61 Gene Expression in Fibroblasts Via Protease-Activated Receptor-1 and p44/42 Mitogen-Activated Protein Kinase–Dependent Signaling Pathway. Arteriosclerosis, Thrombosis, and Vascular Biology 2002, 22 (9) , 1421-1426. https://doi.org/10.1161/01.ATV.0000030200.59331.3F
    69. Nathalie Galéotti, Joël Poncet, Patrick Jouin. Post-Source Decay Analysis of Dolastatin 10 and Dolastatin 15 by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry. European Journal of Mass Spectrometry 2002, 8 (4) , 311-321. https://doi.org/10.1255/ejms.502
    70. Eszter Dömötör, Katalin Bartha, Raymund Machovich, Vera Adam‐Vizi. Protease‐activated receptor‐2 (PAR‐2) in brain microvascular endothelium and its regulation by plasmin and elastase. Journal of Neurochemistry 2002, 80 (5) , 746-754. https://doi.org/10.1046/j.0022-3042.2002.00759.x
    71. Christina Rogalski, Ulf Meyer-Hoffert, Ehrhardt Proksch, Oliver Wiedow. Human Leukocyte Elastase Induces Keratinocyte Proliferation In Vitro and In Vivo. Journal of Investigative Dermatology 2002, 118 (1) , 49-54. https://doi.org/10.1046/j.0022-202x.2001.01650.x
    72. James P. McRedmond, Desmond J. Fitzgerald. A growing set of platelet-activating bacterial proteins. Blood 2002, 99 (1) , 387-388. https://doi.org/10.1182/blood.V99.1.387
    73. Rebecca L. Rich, David G. Myszka. Survey of the year 2000 commercial optical biosensor literature. Journal of Molecular Recognition 2001, 14 (5) , 273-294. https://doi.org/10.1002/jmr.547
    74. Guo Sun, Martin A. Stacey, Matthias Schmidt, Luca Mori, Sabrina Mattoli. Interaction of Mite Allergens Der P3 and Der P9 with Protease-Activated Receptor-2 Expressed by Lung Epithelial Cells. The Journal of Immunology 2001, 167 (2) , 1014-1021. https://doi.org/10.4049/jimmunol.167.2.1014
    75. Tatiana Syrovets, Marina Jendrach, Angela Rohwedder, Almut Schüle, Thomas Simmet. Plasmin-induced expression of cytokines and tissue factor in human monocytes involves AP-1 and IKKβ-mediated NF-κB activation. Blood 2001, 97 (12) , 3941-3950. https://doi.org/10.1182/blood.V97.12.3941
    76. . Current Awareness. Journal of Mass Spectrometry 2001, 107-118. https://doi.org/10.1002/1096-9888(200101)36:1<107::AID-JMS88>3.0.CO;2-Q
    77. David E. Metzler, Carol M. Metzler, David J. Sauke. Transferring Groups by Displacement Reactions. 2001, 589-675. https://doi.org/10.1016/B978-012492543-4/50015-5
    Download PDF
    Go to Biochemistry
    Get e-Alerts
    Get e-Alerts

    Biochemistry

    Cite this: Biochemistry 2000, 39, 35, 10812–10822
    Click to copy citationCitation copied!
    https://doi.org/10.1021/bi0003341
    Published August 10, 2000
    Copyright © 2000 American Chemical Society
    Request reuse permissions

    Article Views

    890

    Altmetric

    -

    Citations

    77
    Learn about these metrics

    Article Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.

    Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.

    The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated.