ACS Publications. Most Trusted. Most Cited. Most Read
My Activity

Plasmin Desensitization of the PAR1 Thrombin Receptor:  Kinetics, Sites of Truncation, and Implications for Thrombolytic Therapy

View Author Information
Molecular Cardiology Research Institute, Division of Hematology/Oncology, New England Medical Center and Departments of Medicine and Biochemistry, Tufts University School of Medicine, Boston, Massachusetts 02111, and Mass Spectrometry Resource, Boston University School of Medicine, Boston, Massachusetts 02118
Cite this: Biochemistry 1999, 38, 14, 4572–4585
Publication Date (Web):March 19, 1999
Copyright © 1999 American Chemical Society

    Article Views





    Read OnlinePDF (199 KB)


    It has been hypothesized that protease-activated receptors may be activated and attenuated by more than one protease. Here, we explore a desensitization mechanism of the PAR1 thrombin receptor by anticoagulant proteases and provide an explanation to the enigma of why plasmin/tissue plasminogen activator (t-PA) can both activate and deactivate platelets prior to thrombin treatment. By using a soluble N-terminal exodomain (TR78) as a model for the full-length receptor, we were able to unambiguously compare cleavage rates and specificities among the serum proteases. Thrombin cleaves TR78 at the R41−S42 peptide bond with a kcat of 120 s-1 and a KM of 16 μM to produce TR62 (residues 42−103). We found that, of the anticoagulant proteases, only plasmin can rapidly truncate the soluble exodomain at the R70/K76/K82 sites located on a linker region that tethers the ligand to the body of the receptor. Plasmin cleavage of the TR78 exodomain is nearly equivalent to that of thrombin cleavage at R41 with similar rates (kcat = 30 s-1) and affinity (KM = 18 μM). Specificity was demonstrated since there is no observed cleavage at the five other potential plasmin-cleavage sites. Plasmin also cleaves the TR78 exodomain at the R41 thrombin-cleavage site generating transiently activated exodomain. We directly demonstrated that plasmin cleaves these same sites in full-length membrane-embedded receptor expressed in yeast and COS7 fibroblasts. The rate of plasmin truncation is similar between the extensively glycosylated COS7-expressed receptor and the nonglycosylated yeast-produced receptor. Mutation of the R70/K76/K82 sites to A70/A76/A82 eliminates plasmin truncation and desensitization of thrombin-dependent Ca2+ signaling and converts PAR1 into a plasmin-activated receptor with full agonist activity for plasmin. Plasmin does not desensitize the Ca2+ response of platelets or COS7 cells to SFLLRN consistent with intermolecular ligand-binding sites being located to the C-terminal side of K82. Truncation of the wild-type receptor at the C-terminal plasmin-cleavage sites removes the N-terminal tethered ligand or preligand, thereby providing an effective pathway for PAR1 desensitization in vivo.

     This work was supported by NIH R29 GM52926-01, the PEW Scholars Program in the Biomedical Sciences, and the American Society of Hematology (A.K.); NIH P41 RR10888, Thermo BioAnalysis Ltd. (C.E.C.), and the Academy of Finland (J.H.).


     To whom correspondence should be addressed at the Division of Hematology/Oncology and Molecular Cardiology Research Institute, Box 832, New England Medical Center. Fax:  (617) 636-4833. E-mail:  [email protected].

     Tufts University School of Medicine.


     Boston University School of Medicine.

     Present Address:  Protein Chemistry Laboratory, Institute of Biotechnology, University of Helsinki, Finland.

    Cited By

    This article is cited by 167 publications.

    1. 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.
    2. Edward L. G. Pryzdial, Alexander Leatherdale, Edward M. Conway. Coagulation and complement: Key innate defense participants in a seamless web. Frontiers in Immunology 2022, 13
    3. Sophie C. Dólleman, Stijn M. Agten, Henri M.H. Spronk, Tilman M. Hackeng, Mettine H.A. Bos, Henri H. Versteeg, Anton Jan van Zonneveld, Hetty C. de Boer. Thrombin in complex with dabigatran can still interact with PAR‐1 via exosite‐I and instigate loss of vascular integrity. Journal of Thrombosis and Haemostasis 2022, 20 (4) , 996-1007.
    4. Yosuke Kanno, En Shu. α2-Antiplasmin as a Potential Therapeutic Target for Systemic Sclerosis. Life 2022, 12 (3) , 396.
    5. Elena Pompili, Valerio De Franchis, Claudia Giampietri, Stefano Leone, Elena De Santis, Francesco Fornai, Lorenzo Fumagalli, Cinzia Fabrizi. Protease Activated Receptor 1 and Its Ligands as Main Regulators of the Regeneration of Peripheral Nerves. Biomolecules 2021, 11 (11) , 1668.
    6. Yohan Seo, Yunkyung Heo, Sungwoo Jo, So‐Hyeon Park, Chulho Lee, Jiwon Chang, Dong‐Kyu Jeon, Tae Gun Kim, Gyoonhee Han, Wan Namkung. Novel positive allosteric modulator of protease‐activated receptor 1 promotes skin wound healing in hairless mice. British Journal of Pharmacology 2021, 178 (17) , 3414-3427.
    7. Michael C. McKelvey, Ryan Brown, Sinéad Ryan, Marcus A. Mall, Sinéad Weldon, Clifford C. Taggart. Proteases, Mucus, and Mucosal Immunity in Chronic Lung Disease. International Journal of Molecular Sciences 2021, 22 (9) , 5018.
    8. Chantal C. Clark, Bernard N. Jukema, Arjan D. Barendrecht, Judith S. Spanjaard, Nikita K. N. Jorritsma, Simone Smits, Steven de Maat, Cor W. Seinen, Sandra Verhoef, Naomi M. J. Parr, Silvie A. E. Sebastian, Arnold C. Koekman, Annet C. W. van Wesel, Harriet M. R. van Goor, Roy Spijkerman, Suzanne H. Bongers, Erhard van der Vries, Stefan Nierkens, Marianne Boes, Leo Koenderman, Karin A. H. Kaasjager, Coen Maas. Thrombotic Events in COVID-19 Are Associated With a Lower Use of Prophylactic Anticoagulation Before Hospitalization and Followed by Decreases in Platelet Reactivity. Frontiers in Medicine 2021, 8
    9. Lahoucine Izem, Katarzyna Bialkowska, Elzbieta Pluskota, Mitali Das, Riku Das, Marvin T. Nieman, Edward F. Plow. Plasminogen‐induced foam cell formation by macrophages occurs through a histone 2B (H2B)‐PAR1 pathway and requires integrity of clathrin‐coated pits. Journal of Thrombosis and Haemostasis 2021, 19 (4) , 941-953.
    10. Arundhasa Chandrabalan, Rithwik Ramachandran. Molecular mechanisms regulating Proteinase‐Activated Receptors (PARs). The FEBS Journal 2021, 288 (8) , 2697-2726.
    11. 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.
    12. Patrick G. Schweickert, Yi Yang, Emily E. White, Gregory M. Cresswell, Bennett D. Elzey, Timothy L. Ratliff, Paritha Arumugam, Silvio Antoniak, Nigel Mackman, Matthew J. Flick, Stephen F. Konieczny. Thrombin‐PAR1 signaling in pancreatic cancer promotes an immunosuppressive microenvironment. Journal of Thrombosis and Haemostasis 2021, 19 (1) , 161-172.
    13. Layla Van Doren, Nga Nguyen, Christopher Garzia, Elizabeth Fletcher, Ryan Stevenson, David Jaramillo, Athan Kuliopulos, Lidija Covic. Lipid Receptor GPR31 (G-Protein–Coupled Receptor 31) Regulates Platelet Reactivity and Thrombosis Without Affecting Hemostasis. Arteriosclerosis, Thrombosis, and Vascular Biology 2020, 16
    14. Xu Han, Marvin T. Nieman. The domino effect triggered by the tethered ligand of the protease activated receptors. Thrombosis Research 2020, 196 , 87-98.
    15. Beate Heissig, Yousef Salama, Satoshi Takahashi, Taro Osada, Koichi Hattori. The multifaceted role of plasminogen in inflammation. Cellular Signalling 2020, 75 , 109761.
    16. Ricardo J. José, Andrew Williams, Ari Manuel, Jeremy S. Brown, Rachel C. Chambers. Targeting coagulation activation in severe COVID-19 pneumonia: lessons from bacterial pneumonia and sepsis. European Respiratory Review 2020, 29 (157) , 200240.
    17. Steven L. Gonias, Carlotta Zampieri. Plasminogen Receptors in Human Malignancies: Effects on Prognosis and Feasibility as Targets for Drug Development. Current Drug Targets 2020, 21 (7) , 647-656.
    18. , A. A. Tykhomyrov, D. D. Zhernosekov, , T. V. Grinenko, . Plasminogen modulates formation and release of platelet angiogenic regulators. The Ukrainian Biochemical Journal 2020, 92 (1) , 31-40.
    19. Orla Willis Fox, Roger J.S. Preston. Molecular basis of protease‐activated receptor 1 signaling diversity. Journal of Thrombosis and Haemostasis 2020, 18 (1) , 6-16.
    20. 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)
    21. Paola Pontecorvi, Michael A. Banki, Carlotta Zampieri, Cristina Zalfa, Pardis Azmoon, Maria Z. Kounnas, Cinzia Marchese, Steven L. Gonias, Elisabetta Mantuano. Fibrinolysis protease receptors promote activation of astrocytes to express pro-inflammatory cytokines. Journal of Neuroinflammation 2019, 16 (1)
    22. 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
    23. Sandra Jastrzebski, Judith Kalinowski, Sehwan Mun, Bongjin Shin, Naga Suresh Adapala, Christian E. Jacome-Galarza, Faryal Mirza, H. Leonardo Aguila, Hicham Drissi, Archana Sanjay, Ernesto Canalis, Sun-Kyeong Lee, Joseph A. Lorenzo. Protease-Activated Receptor 1 Deletion Causes Enhanced Osteoclastogenesis in Response to Inflammatory Signals through a Notch2-Dependent Mechanism. The Journal of Immunology 2019, 203 (1) , 105-116.
    24. Carey Kimmelstiel, Ryan Stevenson, Nga Nguyen, Layla Van Doren, Ping Zhang, James Perkins, Navin K. Kapur, Andrew Weintraub, Vilma Castaneda, Athan Kuliopulos, Lidija Covic. Enhanced potency of prasugrel on protease-activated receptors following bivalirudin treatment for PCI as compared to clopidogrel. Thrombosis Research 2019, 177 , 59-69.
    25. Cristina Zalfa, Pardis Azmoon, Elisabetta Mantuano, Steven L Gonias. Tissue-type plasminogen activator neutralizes LPS but not protease-activated receptor-mediated inflammatory responses to plasmin. Journal of Leukocyte Biology 2019, 105 (4) , 729-740.
    26. Giulia Pontarollo, Florentina Melzow, Christoph Reinhardt. Comment on “Endothelial Protein C Receptor (EPCR), Protease Activated Receptor-1 (PAR-1) and Their Interplay in Cancer Growth and Metastatic Dissemination” Cancers 2019, 11, 51. Cancers 2019, 11 (3) , 374.
    27. Xu Han, Emma G. Bouck, Elizabeth R. Zunica, Amal Arachiche, Marvin T. Nieman. Protease-Activated Receptors. 2019, 243-257.
    28. Tanusree Ray, Dwiprohi Kar, Ananda Pal, Shravanti Mukherjee, Chandrima Das, Amit Pal. Molecular targeting of breast and colon cancer cells by PAR1 mediated apoptosis through a novel pro-apoptotic peptide. Apoptosis 2018, 23 (11-12) , 679-694.
    29. , A. A. Tykhomyrov, D. D. Zhernosekov, , M. M. Guzyk, , V. V. Korsa, , T. V. Grinenko, . Plasminogen modulates formation of reactive oxygen species in human platelets. The Ukrainian Biochemical Journal 2018, 90 (6) , 31-40.
    30. Lidija Covic, Athan Kuliopulos. Protease-Activated Receptor 1 as Therapeutic Target in Breast, Lung, and Ovarian Cancer: Pepducin Approach. International Journal of Molecular Sciences 2018, 19 (8) , 2237.
    31. Aleena Arakaki, Wen-An Pan, JoAnn Trejo. GPCRs in Cancer: Protease-Activated Receptors, Endocytic Adaptors and Signaling. International Journal of Molecular Sciences 2018, 19 (7) , 1886.
    32. David A. Rubenstein, Wei Yin. Platelet‐Activation Mechanisms and Vascular Remodeling. 2018, 1117-1156.
    33. Aleena K.S. Arakaki, Wen-An Pan, Huilan Lin, JoAnn Trejo. The α-arrestin ARRDC3 suppresses breast carcinoma invasion by regulating G protein–coupled receptor lysosomal sorting and signaling. Journal of Biological Chemistry 2018, 293 (9) , 3350-3362.
    34. G.H. Frydman, K.A. Metcalf Pate, A. Vitsky. Platelets and Hemostasis. 2018, 60-113.
    35. Abdou Mousas, Georgios Ntritsos, Ming-Huei Chen, Ci Song, Jennifer E. Huffman, Ioanna Tzoulaki, Paul Elliott, Bruce M. Psaty, , Paul L. Auer, Andrew D. Johnson, Evangelos Evangelou, Guillaume Lettre, Alexander P. Reiner, . Rare coding variants pinpoint genes that control human hematological traits. PLOS Genetics 2017, 13 (8) , e1006925.
    36. Maaike Waasdorp, JanWillem Duitman, C. Arnold Spek. Plasmin reduces fibronectin deposition by mesangial cells in a protease-activated receptor-1 independent manner. Biochemistry and Biophysics Reports 2017, 10 , 152-156.
    37. Manuela Sebastiano, Stefania Momi, Emanuela Falcinelli, Loredana Bury, Marc F. Hoylaerts, Paolo Gresele. A novel mechanism regulating human platelet activation by MMP-2–mediated PAR1 biased signaling. Blood 2017, 129 (7) , 883-895.
    38. Amal Arachiche, Marvin T. Nieman. The Platelet PARs. 2017, 171-185.
    39. Mario Colucci, Nicola Semeraro, Fabrizio Semeraro. Platelets and Fibrinolysis. 2017, 463-487.
    40. Tanusree Ray, Amit Pal. PAR1-Mediated Apoptosis and Tumor Regression of Breast Cancer Cells by Vibrio cholerae Hemagglutinin Protease. 2017, 191-205.
    41. Rithwik Ramachandran, Christophe Altier, Katerina Oikonomopoulou, Morley D. Hollenberg, . Proteinases, Their Extracellular Targets, and Inflammatory Signaling. Pharmacological Reviews 2016, 68 (4) , 1110-1142.
    42. Gerlind Schuldt, Christos Galanis, Andreas Strehl, Meike Hick, Sabine Schiener, Maximilian Lenz, Thomas Deller, Nicola Maggio, Andreas Vlachos. Inhibition of Protease-Activated Receptor 1 Does not Affect Dendritic Homeostasis of Cultured Mouse Dentate Granule Cells. Frontiers in Neuroanatomy 2016, 10
    43. Tanusree Ray, Amit Pal. PAR-1 mediated apoptosis of breast cancer cells by V. cholerae hemagglutinin protease. Apoptosis 2016, 21 (5) , 609-620.
    44. E Yang, J Cisowski, N Nguyen, K O'Callaghan, J Xu, A Agarwal, A Kuliopulos, L Covic. Dysregulated protease activated receptor 1 (PAR1) promotes metastatic phenotype in breast cancer through HMGA2. Oncogene 2016, 35 (12) , 1529-1540.
    45. Thati Madhusudhan, Bryce A. Kerlin, Berend Isermann. The emerging role of coagulation proteases in kidney disease. Nature Reviews Nephrology 2016, 12 (2) , 94-109.
    46. Chi Huu Nguyen, Daniel Senfter, Jose Basilio, Silvio Holzner, Serena Stadler, Sigurd Krieger, Nicole Huttary, Daniela Milovanovic, Katharina Viola, Ingrid Simonitsch-Klupp, Walter Jäger, Rainer de Martin, Georg Krupitza. NF-κB contributes to MMP1 expression in breast cancer spheroids causing paracrine PAR1 activation and disintegrations in the lymph endothelial barrier in vitro. Oncotarget 2015, 6 (36) , 39262-39275.
    47. Ping Zhang, Andrew J. Leger, James D. Baleja, Rajashree Rana, Tiffany Corlin, Nga Nguyen, Georgios Koukos, Andrew Bohm, Lidija Covic, Athan Kuliopulos. Allosteric Activation of a G Protein-coupled Receptor with Cell-penetrating Receptor Mimetics. Journal of Biological Chemistry 2015, 290 (25) , 15785-15798.
    48. Edson T. Yamashiro, Ana K. Oliveira, Eduardo S. Kitano, Milene C. Menezes, Inácio L. Junqueira-de-Azevedo, Adriana F. Paes Leme, Solange M.T. Serrano. Proteoforms of the platelet-aggregating enzyme PA-BJ, a serine proteinase from Bothrops jararaca venom. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics 2014, 1844 (12) , 2068-2076.
    49. Enrico A. Duru, Yuyang Fu, Mark G. Davies. Protease-mediated human smooth muscle cell proliferation by urokinase requires epidermal growth factor receptor transactivation by triple membrane signaling. Journal of Surgical Research 2014, 192 (2) , 254-262.
    50. Alessandra Fazzini, Vanessa D’Antongiovanni, Laura Giusti, Ylenia Da Valle, Federica Ciregia, Ilaria Piano, Antonella Caputo, Anna Maria D’Ursi, Claudia Gargini, Antonio Lucacchini, Maria Rosa Mazzoni, . Altered Protease–Activated Receptor-1 Expression and Signaling in a Malignant Pleural Mesothelioma Cell Line, NCI-H28, with Homozygous Deletion of the β-Catenin Gene. PLoS ONE 2014, 9 (11) , e111550.
    51. Maria Adele Alberelli, Erica De Candia. Functional role of protease activated receptors in vascular biology. Vascular Pharmacology 2014, 62 (2) , 72-81.
    52. Be'eri Niego, Robert L Medcalf. Plasmin-Dependent Modulation of the Blood–Brain Barrier: A Major Consideration during tPA-Induced Thrombolysis?. Journal of Cerebral Blood Flow & Metabolism 2014, 34 (8) , 1283-1296.
    53. Peishen Zhao, Matthew Metcalf, Nigel W. Bunnett. Biased Signaling of Protease-Activated Receptors. Frontiers in Endocrinology 2014, 5
    54. Tejminder Sidhu, Shauna French, Justin Hamilton. Differential Signaling by Protease-Activated Receptors: Implications for Therapeutic Targeting. International Journal of Molecular Sciences 2014, 15 (4) , 6169-6183.
    55. Silvia Sedda. Proteinase activated-receptors-associated signaling in the control of gastric cancer. World Journal of Gastroenterology 2014, 20 (34) , 11977.
    56. Y. Miyake, C.N. D'Alessandro‐Gabazza, T. Takagi, M. Naito, O. Hataji, H. Nakahara, H. Yuda, H. Fujimoto, H. Kobayashi, T. Yasuma, M. Toda, T. Kobayashi, Y. Yano, J. Morser, O. Taguchi, E.C. Gabazza. Dose‐dependent differential effects of thrombin in allergic bronchial asthma. Journal of Thrombosis and Haemostasis 2013, 11 (10) , 1903-1915.
    57. Eduardo S. Kitano, Thalita C. Garcia, Milene C. Menezes, Alexandre K. Tashima, André Zelanis, Solange M.T. Serrano. Cotiarinase is a novel prothrombin activator from the venom of Bothrops cotiara. Biochimie 2013, 95 (8) , 1655-1659.
    58. Wataru Nemoto, Tasuku Sato, Osamu Nakagawasai, Fukie Yaoita, Jerzy Silberring, Takeshi Tadano, Koichi Tan-No. Phenylmethanesulfonyl fluoride, a serine protease inhibitor, suppresses naloxone-precipitated withdrawal jumping in morphine-dependent mice. Neuropeptides 2013, 47 (3) , 187-191.
    59. Karyn M. Austin, Lidija Covic, Athan Kuliopulos. Matrix metalloproteases and PAR1 activation. Blood 2013, 121 (3) , 431-439.
    60. Ping Zhang, Lidija Covic, Athan Kuliopulos. Protease-Activated Receptors. 2013, 249-259.
    61. Henri H. Versteeg, Johan W. M. Heemskerk, Marcel Levi, Pieter H. Reitsma. New Fundamentals in Hemostasis. Physiological Reviews 2013, 93 (1) , 327-358.
    62. M. Mark Stanton, Lisa K. Nelson, Hallgrimur Benediktsson, Morley D. Hollenberg, Andre G. Buret, Howard Ceri. Proteinase-Activated Receptor-1 and Immunomodulatory Effects of a PAR1-Activating Peptide in a Mouse Model of Prostatitis. Mediators of Inflammation 2013, 2013 , 1-12.
    63. Antoine G. Almonte, Laura H. Qadri, Faraz A. Sultan, Jennifer A. Watson, Daniel J. Mount, Gavin Rumbaugh, J. David Sweatt. Protease‐activated receptor‐1 modulates hippocampal memory formation and synaptic plasticity. Journal of Neurochemistry 2013, 124 (1) , 109-122.
    64. Kukiat Tudpor, Sergio Laínez, Arjan J. Kwakernaak, Nadezda V. Kovalevskaya, Sjoerd Verkaart, Siebe van Genesen, Annemiete van der Kemp, Gerjan Navis, René J.M. Bindels, Joost G.J. Hoenderop. Urinary Plasmin Inhibits TRPV5 in Nephrotic-Range Proteinuria. Journal of the American Society of Nephrology 2012, 23 (11) , 1824-1834.
    65. Emilia S. Olson, Michael A. Whitney, Beth Friedman, Todd A. Aguilera, Jessica L. Crisp, Fred M. Baik, Tao Jiang, Stephen M. Baird, Sotirios Tsimikas, Roger Y. Tsien, Quyen T. Nguyen. In vivo fluorescence imaging of atherosclerotic plaques with activatable cell-penetrating peptides targeting thrombin activity. Integrative Biology 2012, 4 (6) , 595-605.
    66. Tatiana Syrovets, Oleg Lunov, Thomas Simmet. Plasmin as a proinflammatory cell activator. Journal of Leukocyte Biology 2012, 92 (3) , 509-519.
    67. María de la Fuente, Daniel N. Noble, Sheetal Verma, Marvin T. Nieman. Mapping Human Protease-activated Receptor 4 (PAR4) Homodimer Interface to Transmembrane Helix 4. Journal of Biological Chemistry 2012, 287 (13) , 10414-10423.
    68. Katerina Oikonomopoulou, Daniel Ricklin, Peter A. Ward, John D. Lambris. Interactions between coagulation and complement—their role in inflammation. Seminars in Immunopathology 2012, 34 (1) , 151-165.
    69. 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.
    70. Edwin S. Gershom, Amanda L. Vanden Hoek, Scott C. Meixner, Michael R. Sutherland, Edward L.G. Pryzdial. Herpesviruses enhance fibrin clot lysis. Thrombosis and Haemostasis 2012, 107 (04) , 760-768.
    71. Bo Chen. Thrombin in Ischemic Stroke Targeting. 2012, 189-204.
    72. Leila M. Sevigny, Karyn M. Austin, Ping Zhang, Shogo Kasuda, Georgios Koukos, Sheida Sharifi, Lidija Covic, Athan Kuliopulos. Protease-Activated Receptor-2 Modulates Protease-Activated Receptor-1–Driven Neointimal Hyperplasia. Arteriosclerosis, Thrombosis, and Vascular Biology 2011, 31 (12)
    73. Troy A. McEachron, Frank C. Church, Nigel Mackman. Regulation of thrombin-induced plasminogen activator inhibitor-1 in 4T1 murine breast cancer cells. Blood Coagulation & Fibrinolysis 2011, 22 (7) , 576-582.
    74. Antoine G. Almonte, J. David Sweatt. Serine proteases, serine protease inhibitors, and protease-activated receptors: Roles in synaptic function and behavior. Brain Research 2011, 1407 , 107-122.
    75. 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.
    76. Jaroslaw Cisowski, Katie O'Callaghan, Athan Kuliopulos, John Yang, Nga Nguyen, Qing Deng, Eric Yang, Michael Fogel, Sarah Tressel, Caitlin Foley, Anika Agarwal, Stephen W. Hunt, Tom McMurry, Larry Brinckerhoff, Lidija Covic. Targeting Protease-Activated Receptor-1 with Cell-Penetrating Pepducins in Lung Cancer. The American Journal of Pathology 2011, 179 (1) , 513-523.
    77. Sarah L. Tressel, Nicole C. Kaneider, Shogo Kasuda, Caitlin Foley, Georgios Koukos, Karyn Austin, Anika Agarwal, Lidija Covic, Steven M. Opal, Athan Kuliopulos. A matrix metalloprotease‐PAR1 system regulates vascular integrity, systemic inflammation and death in sepsis. EMBO Molecular Medicine 2011, 3 (7) , 370-384.
    78. 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.
    79. Georgios Koukos, Leila Sevigny, Ping Zhang, Lidija Covic, Athan Kuliopulos. Serine and metalloprotease signaling through PAR1 in arterial thrombosis and vascular injury. IUBMB Life 2011, 63 (6) , 412-418.
    80. 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.
    81. Fiona A. Russell, Jason J. McDougall. Proteinase-Activated Receptors and Arthritis. 2011, 217-242.
    82. Morley D. Hollenberg, Kristina K. Hansen, Koichiro Mihara, Rithwik Ramachandran. Proteolytic Enzymes and Cell Signaling: Pharmacological Lessons. 2011, 1-25.
    83. Daisuke Fujimoto, Yasuo Hirono, Takanori Goi, Kanji Katayama, Shigeru Matsukawa, Akio Yamaguchi. The activation of Proteinase-Activated Receptor-1 (PAR1) mediates gastric cancer cell proliferation and invasion. BMC Cancer 2010, 10 (1)
    84. Antonio G. Soto, JoAnn Trejo. N-Linked Glycosylation of Protease-activated Receptor-1 Second Extracellular Loop. Journal of Biological Chemistry 2010, 285 (24) , 18781-18793.
    85. Unice JK Soh, Michael R Dores, Buxin Chen, JoAnn Trejo. Signal transduction by protease‐activated receptors. British Journal of Pharmacology 2010, 160 (2) , 191-203.
    86. Steven Swift, Jian Xu, Vishal Trivedi, Karyn M. Austin, Sarah L. Tressel, Lei Zhang, Lidija Covic, Athan Kuliopulos. A Novel Protease-activated Receptor-1 Interactor, Bicaudal D1, Regulates G Protein Signaling and Internalization. Journal of Biological Chemistry 2010, 285 (15) , 11402-11410.
    87. Li‐Mei Chen, Meghan L. Hatfield, Ya‐Yuan Fu, Karl X. Chai. Prostasin regulates iNOS and cyclin D1 expression by modulating protease‐activated receptor‐2 signaling in prostate epithelial cells. The Prostate 2009, 69 (16) , 1790-1801.
    88. Eric Yang, Adrienne Boire, Anika Agarwal, Nga Nguyen, Katie O'Callaghan, Powen Tu, Athan Kuliopulos, Lidija Covic. Blockade of PAR1 Signaling with Cell-Penetrating Pepducins Inhibits Akt Survival Pathways in Breast Cancer Cells and Suppresses Tumor Survival and Metastasis. Cancer Research 2009, 69 (15) , 6223-6231.
    89. 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.
    90. Vishal Trivedi, Adrienne Boire, Boris Tchernychev, Nicole C. Kaneider, Andrew J. Leger, Katie O'Callaghan, Lidija Covic, Athan Kuliopulos. Platelet Matrix Metalloprotease-1 Mediates Thrombogenesis by Activating PAR1 at a Cryptic Ligand Site. Cell 2009, 137 (2) , 332-343.
    91. Rithwik Ramachandran, Mahmoud El-Daly, Mahmoud Saifeddine, Morley D. Hollenberg*. Thrombin: To PAR or Not to PAR, and the Regulation of Inflammation. 2009, 19-46.
    92. JoAnn Trejo. Regulation of Thrombin Receptor Signaling. 2009, 47-61.
    93. Matthias Riewald. Thrombin-Activated Protein C: Integrated to Regulate Vascular Physiology. 2009, 63-80.
    94. Chris I. Jones, David A. Payne, Paul D. Hayes, A. Ross Naylor, Peter R.F. Bell, Mathew M. Thompson, Alison H. Goodall. The antithrombotic effect of dextran-40 in man is due to enhanced fibrinolysis in vivo. Journal of Vascular Surgery 2008, 48 (3) , 715-722.
    95. Anika Agarwal, Lidija Covic, Leila M. Sevigny, Nicole C. Kaneider, Katherine Lazarides, Gissou Azabdaftari, Sheida Sharifi, Athan Kuliopulos. Targeting a metalloprotease-PAR1 signaling system with cell-penetrating pepducins inhibits angiogenesis, ascites, and progression of ovarian cancer. Molecular Cancer Therapeutics 2008, 7 (9) , 2746-2757.
    96. Kristina K. Hansen, Katerina Oikonomopoulou, Amos Baruch, Rithwik Ramachandran, Paul Beck, Eleftherios P. Diamandis, Morley D. Hollenberg. Proteinases as hormones: targets and mechanisms for proteolytic signaling. Biological Chemistry 2008, 0 (ja) , 080808065704617-30.
    97. Kristina K. Hansen, Katerina Oikonomopoulou, Amos Baruch, Rithwik Ramachandran, Paul Beck, Eleftherios P. Diamandis, Morley D. Hollenberg. Proteinases as hormones: targets and mechanisms for proteolytic signaling. Biological Chemistry 2008, 389 (8) , 971-982.
    98. Chris Jackson, Kaley Whitmont, Sara Tritton, Lyn March, Philip Sambrook, Meilang Xue. New therapeutic applications for the anticoagulant, activated protein C. Expert Opinion on Biological Therapy 2008, 8 (8) , 1109-1122.
    99. P Arora, B D Cuevas, A Russo, G L Johnson, J Trejo. Persistent transactivation of EGFR and ErbB2/HER2 by protease-activated receptor-1 promotes breast carcinoma cell invasion. Oncogene 2008, 27 (32) , 4434-4445.
    100. 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.
    Load all citations

    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.

    Your Mendeley pairing has expired. Please reconnect