Research Topics
Genomes and Genes
| par 1 receptorSummarySummary: A thrombin receptor subtype that couples to HETEROTRIMERIC GTP-BINDING PROTEINS resulting in the activation of a variety of signaling mechanisms including decreased intracellular CYCLIC AMP, increased PHOSPHOLIPASE C and increased PHOSPHOLIPASE A2. Top Publications
Research Grants
| Scientific Experts
|
Detail Information
Publications
The pattern of expression of protease-activated receptors (PARs) during early trophoblast developmentSharona Cohen Even-Ram
Department of Oncology, Pathology, Hadassah University Hospital, Jerusalem, Israel
J Pathol 200:47-52. 2003..Together, our data suggest the involvement of PAR1 and PAR3 in restricted and unrestricted pathological trophoblast invasion...
Thrombin responses in human endothelial cells. Contributions from receptors other than PAR1 include the transactivation of PAR2 by thrombin-cleaved PAR1P J O'Brien
Departments of Medicine and Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 275:13502-9. 2000..Such transactivation may limit the effectiveness of PAR1 antagonists, which compete with the tethered ligand domain rather than preventing PAR1 cleavage...
Role of the PAR1 receptor 8th helix in signaling: the 7-8-1 receptor activation mechanismSteven Swift
Molecular Oncology Research Institute, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
J Biol Chem 281:4109-16. 2006..This "7-8-1" interaction network was found to be prevalent in G protein-coupled receptors involved in endothelial signaling and angiogenesis...
The cytoprotective protein C pathwayLaurent O Mosnier
Department of Molecular and Experimental Medicine MEM 180, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, USA
Blood 109:3161-72. 2007....
Termination of protease-activated receptor-1 signaling by beta-arrestins is independent of receptor phosphorylationChii-Heui Chen
Department of Pharmacology, Cardiovascular Biology Center, Lineberger Comprehensive Cancer Center, School of Medicine, University of North Carolina, Chapel Hill 27599-7365, USA
J Biol Chem 279:10020-31. 2004..These findings reveal a new level of complexity in the regulation of protease-activated GPCR signaling...
Differential expression of protease activated receptor 1 (Par1) and pY397FAK in benign and malignant human ovarian tissue samplesSorina Grisaru-Granovsky
Department of Oncology, Hadassah Hebrew University Hospital, Jerusalem, Israel
Int J Cancer 113:372-8. 2005..Altogether our data suggest that hPar1 and FAK cooperate to promote ovarian cancer malignancy...
Protease-activated receptor-1 (hPar1), a survival factor eliciting tumor progressionZaidoun Salah
Department of Oncology, Hadassah Hebrew University Hospital, P O Box 12000, Jerusalem 91120, Israel
Mol Cancer Res 5:229-40. 2007..We conclude that whereas PAR1 gene expression correlates with tumor progression, its neutralization effectively initiates an apoptotic pathway leading at least in part to significantly reduced tumor formation...
Protease-activated receptors 1 and 4 mediate thrombin signaling in endothelial cellsHiroshi Kataoka
Cardiovascular Research Institute and Department of Medicine and Celluar and Molecular Pharmacology, University of California, San Francisco, 94143, USA
Blood 102:3224-31. 2003..These receptors serve at least partially redundant roles in endothelial cells in vitro and in vivo and together are necessary for the thrombin responses measured...
Extracellular mediators in atherosclerosis and thrombosis: lessons from thrombin receptor knockout miceChristopher D Major
Johnson and Johnson Pharmaceutical Research and Development, L.L.C, Spring House, PA 19477-0776, USA
Arterioscler Thromb Vasc Biol 23:931-9. 2003....
Human protease-activated receptor 1 expression in malignant epithelia: a role in invasivenessYong Jun Yin
Department of Oncology, Hadassah University Hospital, POB 12000, Jerusalem 91120, Israel
Arterioscler Thromb Vasc Biol 23:940-4. 2003..PAR1 induces angiogenesis in animal models in vivo and exhibits an oncogenic phenotype of enhanced ductal complexity when overexpressed in mouse mammary glands...
Expression of protease-activated receptor-1, -2, -3, and -4 in control and experimentally inflamed mouse bladderMichael R D'Andrea
Johnson and Johnson Pharmaceutical Research and Development, Spring House, Pennsylvania, USA
Am J Pathol 162:907-23. 2003..It is timely to understand the role of tryptase signaling and PARs in the context of bladder biology...
Activated protein C blocks p53-mediated apoptosis in ischemic human brain endothelium and is neuroprotectiveTong Cheng
Frank P Smith Neurosurgical Research Laboratory, Department of Neurosurgery and Center for Aging and Developmental Biology, Division of Neurovascular Biology, University of Rochester Medical Center, Rochester, New York, USA
Nat Med 9:338-42. 2003..9). Moreover, the in vivo neuroprotective effects of low-dose mouse APC seemed to be independent of its anti-coagulant activity. Thus, APC protects the brain from ischemic injury by acting directly on brain cells...
Unproductive cleavage and the inactivation of protease-activated receptor-1 by trypsin in vascular endothelial cellsTetsuzo Nakayama
Division of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, 3 1 1 Maidashi, Higashi ku, Fukuoka 812 8582, Japan
Br J Pharmacol 138:121-30. 2003..05) attenuated by the preceding stimulation with thrombin but not trypsin. 5 In conclusion, trypsin cleaved PAR1 but did not activate it in the endothelial cells. Moreover, the trypsin-cleaved PAR1 was no longer responsive to thrombin...
Protease-activated receptors: the role of cell-surface proteolysis in signallingGraeme S Cottrell
Department of Surgery, University of California at San Francisco, 521 Parnassus Avenue, San Francisco, CA 94143-0660, USA
Essays Biochem 38:169-83. 2002..Therefore, selective antagonists or agonists of these receptors may be useful therapeutic agents for the treatment of human diseases...
Phospholipid metabolite production in human urothelial cells after protease-activated receptor cleavageAlice Rickard
Department of Pathology, St Louis University School of Medicine, St Louis, Missouri 63104, USA
Am J Physiol Renal Physiol 283:F944-51. 2002..Thus stimulation of PAR-1 or PAR-2 on HUR leads to iPLA(2)-catalyzed phospholipid hydrolysis, resulting in the production of metabolites that may mediate inflammation or provide cytoprotection to the bladder...
'Role reversal' for the receptor PAR1 in sepsis-induced vascular damageNicole C Kaneider
Departments of Medicine and Biochemistry, Molecular Oncology Research Institute, New England Medical Center and Tufts University School of Medicine, Boston, Massachusetts 02111, USA
Nat Immunol 8:1303-12. 2007..Unexpectedly, we found that the protective effects of PAR1 required transactivation of PAR2 signaling pathways. Our results suggest therapeutics that selectively activate PAR1-PAR2 complexes may be beneficial in the treatment of sepsis...
Galpha(q) and Gbetagamma regulate PAR-1 signaling of thrombin-induced NF-kappaB activation and ICAM-1 transcription in endothelial cellsArshad Rahman
Department of Pharmacology, College of Medicine, The University of Illinois, Chicago, Ill 60612 7343, USA
Circ Res 91:398-405. 2002..These results support a model in which ligation of PAR-1 induces NF-kappaB activation and ICAM-1 transcription by the engagement of parallel Galphaq/PKC-delta and Gbetagamma/PI3-kinase pathways that converge at Akt...
Protease-activated receptor-3 (PAR3) regulates PAR1 signaling by receptor dimerizationJoseph N McLaughlin
Department of Pharmacology and Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, IL 60612, USA
Proc Natl Acad Sci U S A 104:5662-7. 2007..Because PAR3 is a critical determinant of PAR1 function, targeting of PAR3 may mitigate the effects of PAR1 in activating endothelial responses such as vascular inflammation...
A tyrosine-based sorting signal regulates intracellular trafficking of protease-activated receptor-1: multiple regulatory mechanisms for agonist-induced G protein-coupled receptor internalizationMay M Paing
Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 7365, USA
J Biol Chem 279:21938-47. 2004..This study is the first to describe a function for a tyrosine-based motif, YXX, in GPCR internalization and reveal novel complexities in the regulation of GPCR trafficking...
Tethered ligand-derived peptides of proteinase-activated receptor 3 (PAR3) activate PAR1 and PAR2 in Jurkat T cellsKristina K Hansen
Department of Pharmacology and Therapeutics, University of Calgary Faculty of Medicine, Calgary, Alberta, Canada
Immunology 112:183-90. 2004....
Protease-activated receptor-2 is essential for factor VIIa and Xa-induced signaling, migration, and invasion of breast cancer cellsDionne R Morris
Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7365, USA
Cancer Res 66:307-14. 2006....
Functional selectivity of G protein signaling by agonist peptides and thrombin for the protease-activated receptor-1Joseph N McLaughlin
Department of Pharmacology, Vanderbilt University Medical Center, Vanderbilt University, Nashville, Tennessee 37232, USA
J Biol Chem 280:25048-59. 2005..This model provides an estimate that peptide activation alters receptor/G protein binding to favor Galpha(q) activation over Galpha(12/13) by approximately 800-fold...
An essential role for SNX1 in lysosomal sorting of protease-activated receptor-1: evidence for retromer-, Hrs-, and Tsg101-independent functions of sorting nexinsAnuradha Gullapalli
Department of Pharmacology, University of North Carolina at Chapel Hill, NC 27599 7365, USA
Mol Biol Cell 17:1228-38. 2006..Together, our findings establish an essential role for endogenous SNX1 in sorting activated PAR1 to a distinct lysosomal degradative pathway that is independent of retromer, Hrs, and Tsg101...
Absence of proteinase-activated receptor-1 signaling affords protection from bleomycin-induced lung inflammation and fibrosisDavid C J Howell
Centre for Respiratory Research, University College London, The Rayne Institute, 5 University Street, London WC1E 6JJ, United Kingdom
Am J Pathol 166:1353-65. 2005....
Characterization and functional activity of thrombin receptors in the human lensColin James
School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK
Invest Ophthalmol Vis Sci 46:925-32. 2005..PAR3 mRNA was also detected, but the receptor itself, if present, was not coupled to the above signaling elements...
PAR1 is a matrix metalloprotease-1 receptor that promotes invasion and tumorigenesis of breast cancer cellsAdrienne Boire
Molecular Oncology Research Institute, Tufts New England Medical Center, Boston, Massachusetts 02111, USA
Cell 120:303-13. 2005..These results demonstrate that MMP-1 in the stromal-tumor microenvironment can alter the behavior of cancer cells through PAR1 to promote cell migration and invasion...
Protease-activated receptor 1: a role in prostate cancer metastasisTa-Chun Yuan
Department of Biochemistry, University of Nebraska Medical Center, Omaha, NE 68198-5870, USA
Clin Prostate Cancer 3:189-91. 2004....
Endothelial barrier protection by activated protein C through PAR1-dependent sphingosine 1-phosphate receptor-1 crossactivationClemens Feistritzer
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
Blood 105:3178-84. 2005....
Protease-activated receptor stimulation activates a Ca2+-independent phospholipase A2 in bladder microvascular endothelial cellsAlice Rickard
Dept of Pathology, Saint Louis Univ School of Medicine, 1402 S Grand Blvd, St Louis, MO 63104, USA
Am J Physiol Renal Physiol 288:F714-21. 2005....
A role for proteinase-activated receptor-1 in inflammatory bowel diseasesNathalie Vergnolle
Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, Canada
J Clin Invest 114:1444-56. 2004....
Thrombin induces endocytosis of endoglin and type-II TGF-beta receptor and down-regulation of TGF-beta signaling in endothelial cellsHua Tang
Department of Biochemistry, The University of Texas Health Center at Tyler, 11937 US Highway 271, Tyler, TX 75708, USA
Blood 105:1977-85. 2005..Since TGF-beta plays a crucial role in the resolution phase of angiogenesis, the down-regulation of TGF-beta signaling by thrombin-PAR1 pathway may provide a new insight into the mechanism of the proangiogenic effect of thrombin...
von Hippel-Lindau tumor suppressor protein stimulation by thrombin involves RhoA activationSandra Turcotte
, , , ,
Int J Cancer 112:777-86. 2004..Together, these results demonstrate that thrombin induces both pVHL expression via PAR1/RhoA activation as well as the stimulation of renal cancer cell invasion suggesting a role for thrombin in tumor invasion...
Thrombin/thrombin receptor (PAR-1)-mediated induction of IL-8 and VEGF expression in prostate cancer cellsJian Liu
University of Rostock, Institute of Clinical Chemistry and Laboratory Medicine, Ernst-Heydemann-Str. 6, D-18057 Rostock, Germany
Biochem Biophys Res Commun 343:183-9. 2006..The results suggest that the thrombin/PAR-1 system upregulates cytokines in prostate cancer cells which in turn may contribute to the progression of prostate cancer...
Clathrin adaptor AP2 regulates thrombin receptor constitutive internalization and endothelial cell resensitizationMay M Paing
Department of Pharmacology, University of North Carolina at Chapel Hill, 1106 Mary Ellen Jones Bldg, Chapel Hill, NC 27599 7365 USA
Mol Cell Biol 26:3231-42. 2006..Our findings establish a novel role for AP2 in direct regulation of PAR1 trafficking, a process critically important to the temporal and spatial aspects of thrombin signaling...
Cysteinyl leukotriene 2 receptor and protease-activated receptor 1 activate strongly correlated early genes in human endothelial cellsBarbara Uzonyi
Institute for Vascular Medicine aud Institute for Medical Statistics, Computer Sciences, and Documentation, Friedrich Schiller University, Bachstrasse 18, 07743 Jena, Germany
Proc Natl Acad Sci U S A 103:6326-31. 2006..These data show that cysLT2-R activation results in a proinflammatory EC phenotype. Because LTD4 and thrombin are likely to be formed concomitantly in vivo, cysLT2-R and PAR-1 may cooperate to augment vascular injury...
Amplification of MMP-2 and MMP-9 production by prostate cancer cell lines via activation of protease-activated receptorsSusan R Wilson
School of Pharmacy, Medical Biology Centre, Queens University Belfast, 97 Lisburn Road, Belfast, United Kingdom
Prostate 60:168-74. 2004..CONCLUSION: Preliminary studies show the activation of PAR-1 or PAR-2 produced increased levels of MMP-2 and MMP-9 activity in prostate cancer cell lines, indicating their potential role in the metastasis of prostate cancer cells...
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 cellsNithiananthan Asokananthan
Division of Inflammation and Infectious Diseases, Department of Microbiology, Asthma and Allergy Research Institute, University of Western Australia, Nedlands, Western Australia, Australia
J Immunol 168:3577-85. 2002..Combined, these data suggest an important role for PAR in the modulation of inflammation in the lung...
Activation of sphingosine kinase-1 reverses the increase in lung vascular permeability through sphingosine-1-phosphate receptor signaling in endothelial cellsMohammad Tauseef
Department of Pharmacology and Center for Lung and Vascular Biology, College of Medicine, University of Illinois, Chicago, IL 60612, USA
Circ Res 103:1164-72. 2008..Our results suggest the crucial role of activation of the SPHK1-->S1P-->S1P1 signaling pathway in response to inflammatory mediators in endothelial cells in regulating endothelial barrier homeostasis...
Agonists of proteinase-activated receptor 1 induce plasma extravasation by a neurogenic mechanismL de Garavilla
The R.W. Johnson Pharmaceutical Research Institute, Spring House, Pennsylvania, USA
Br J Pharmacol 133:975-87. 2001..In intact tissues, neurogenic mechanisms are predominantly responsible for PAR1-induced oedema...
Activation and inhibition of G protein-coupled receptors by cell-penetrating membrane-tethered peptidesLidija Covic
Molecular Cardiology Research Institute, Division of Hematology/Oncology, New England Medical Center, 750 Washington Street, Boston, MA 02111, USA
Proc Natl Acad Sci U S A 99:643-8. 2002..Construction of such peptide-lipid conjugates constitutes a new molecular strategy for the development of therapeutics targeted to the receptor-effector interface...
Protease-activated receptors: sentries for inflammation?T M Cocks
Department of Pharmacology, The University of Melbourne, Parkville, Victoria 3010, Australia
Trends Pharmacol Sci 21:103-8. 2000..In this article, the ways in which the distribution and function of PARs could be harnessed by pharmacologists as novel anti-inflammatory therapeutic strategies are discussed...
Review article: proteinase-activated receptors - novel signals for gastrointestinal pathophysiologyN Vergnolle
Department of Pharmacology and Therapeutics, Faculty of Medicine, The University of Calgary, Calgary, Alberta, Canada
Aliment Pharmacol Ther 14:257-66. 2000..Nonetheless, the use of PAR agonists has already highlighted new potential functions for proteinases in the gastrointestinal tract, thus the control of PAR activation might represent a promising therapeutic target...
A role for thrombin receptor signaling in endothelial cells during embryonic developmentC T Griffin
Cardiovascular Research Institute, University of California at San Francisco UCSF, San Francisco, California 94143
Science 293:1666-70. 2001....
How the protease thrombin talks to cellsS R Coughlin
Cardiovascular Research Institute, Department of Medicine, University of California, San Francisco, CA 94143 0130, USA
Proc Natl Acad Sci U S A 96:11023-7. 1999..PAR2 is activated by trypsin and by trypsin-like proteases but not by thrombin. Recent studies with knockout mice, receptor-activating peptides, and blocking antibodies are beginning to define the role of these receptors in vivo...
Abrogation of thrombin-induced increase in pulmonary microvascular permeability in PAR-1 knockout miceS M Vogel
Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois 60612, USA
Physiol Genomics 4:137-145. 2000..The results indicate that the PAR-1 receptor is critical in mediating the permeability-increasing and vasoconstrictor effects of thrombin in pulmonary microvessels...
Protease-activated receptors in inflammation, neuronal signaling and painN Vergnolle
Mucosal Inflammation Research Group, Dept of Pharmacology and Therapeutics, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Alberta, T2N 4N1, Calgary, Canada
Trends Pharmacol Sci 22:146-52. 2001..Thus, the list of potential roles for PARs has lengthened considerably and their physiological course of action might be much broader than initially anticipated...
Tumor cell invasion is promoted by activation of protease activated receptor-1 in cooperation with the alpha vbeta 5 integrinS C Even-Ram
Departments of Oncology and Pharmacology at the Hadassah Hebrew University Hospital, Jerusalem 91120, Israel, The Department of Hematology, Medical Center, Tel Aviv 64239, Israel
J Biol Chem 276:10952-62. 2001..We propose that the activation of PAR1 may lead to a novel cooperation with the alpha(v)beta(5) integrin that supports tumor cell invasion...
Regulated shedding of PAR1 N-terminal exodomain from endothelial cellsMatthew J Ludeman
Cardiovascular Research Institute, University of California, San Francisco 94143 0130, USA
J Biol Chem 279:18592-9. 2004..Nonetheless, regulated shedding of G protein-coupled receptors represents a new mechanism by which signaling by this important class of receptors might be modulated...
Proteinase-activated receptorsS R Macfarlane
Department of Physiology and Pharmacology, University of Strathclyde, Strathclyde Institute for Biomedical Sciences, Glasgow, United Kingdom
Pharmacol Rev 53:245-82. 2001..The future identification of other PARs and their modes of activation are an important future direction for this expanding field of study...
Protease-activated receptor (PAR) 1 but not PAR2 or PAR4 mediates endothelium-dependent relaxation to thrombin and trypsin in human pulmonary arteriesJ R Hamilton
Department of Pharmacology, University of Melbourne, Victoria, Australia
J Cardiovasc Pharmacol 38:108-19. 2001..We conclude that human pulmonary arteries express PAR1, PAR2, and PAR4, but that only PAR1, or a PAR1-like receptor, is coupled to endothelium-dependent relaxation...
Protease-activated receptor 1 mediates thrombin-dependent, cell-mediated renal inflammation in crescentic glomerulonephritisM A Cunningham
Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, 3168 Victoria, Australia
J Exp Med 191:455-62. 2000..These results indicate that activation of PAR-1 by thrombin or TRAP amplifies crescentic GN. Thus, in addition to its procoagulant role, thrombin has proinflammatory, PAR-1-dependent effects that augment inflammatory renal injury...
PAR1 thrombin receptor-G protein interactions. Separation of binding and coupling determinants in the galpha subunitS Swift
Molecular Cardiology Research Institute, Division of Hematology, New England Medical Center, Boston, Massachusetts 02111, USA
J Biol Chem 275:2627-35. 2000....
Persistent transactivation of EGFR and ErbB2/HER2 by protease-activated receptor-1 promotes breast carcinoma cell invasionP Arora
Department of Pharmacology, Lineberger Comprehensive Cancer Center, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Oncogene 27:4434-45. 2008..These studies reveal a critical role for PAR1, a receptor activated by tumor-generated proteases, in hyperactivation of ErbB signaling that promotes breast carcinoma cell invasion...
Interleukin-6 production by endothelial cells via stimulation of protease-activated receptors is amplified by endotoxin and tumor necrosis factor-alphaL Chi
Division of Allergy, Clinical Immunology and Rheumatology, Department of Medicine, University of Kansas Medical Center, Kansas City, KS 66160-7317, USA
J Interferon Cytokine Res 21:231-40. 2001..The results demonstrate significant potentiation of PAR-induced signaling by LPS and TNF-alpha and indicate the potential cooperation of proteases and inflammatory stimuli in amplifying vascular inflammation...
Reaction of mast cell proteases tryptase and chymase with protease activated receptors (PARs) on keratinocytes and fibroblastsN M Schechter
Department of Dermatology, University of Pennsylvania, Philadelphia 19104 6142, USA
J Cell Physiol 176:365-73. 1998..These results suggest that the proteases tryptase and chymase secreted from mast cells in skin may affect the behavior of surrounding cells by the hydrolysis of PARs expressed by these cells...
Distinct roles of protease-activated receptors in signal transduction regulation of endothelial nitric oxide synthaseHiroyuki Suzuki
Cardiovascular Research Center and Department of Physiology, Temple University School of Medicine, 3420 N Broad St, Philadelphia, PA 19140, USA
Hypertension 53:182-8. 2009....
Genetic evidence that protease-activated receptors mediate factor Xa signaling in endothelial cellsEric Camerer
Cardiovascular Research Institute, University of California, San Francisco, California 94143, USA
J Biol Chem 277:16081-7. 2002..This information is critical for the design and interpretation of knockout mouse studies to probe the possible roles of Xa signaling in vivo...
Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombinM L Kahn
Cardiovascular Research Institute and Daiichi Research Center, University of California San Francisco, San Francisco, California 94143 0130, USA
J Clin Invest 103:879-87. 1999..These observations suggest that PAR1 and PAR4 account for most, if not all, thrombin signaling in platelets and that antagonists that block these receptors might be useful antithrombotic agents...
Differential expression of protease-activated receptors-1 and -2 in stromal fibroblasts of normal, benign, and malignant human tissuesM R D'Andrea
Drug Discovery, The R W Johnson Pharmaceutical Research Institute, Spring House, Pennsylvania 19477, USA
Am J Pathol 158:2031-41. 2001..PAR-1 and PAR-2 in the cells forming the tumor microenvironment suggest that these receptors mediate the signaling of secreted thrombin and trypsin in the processes of cellular metastasis...
Plasmin desensitization of the PAR1 thrombin receptor: kinetics, sites of truncation, and implications for thrombolytic therapyA Kuliopulos
Molecular Cardiology Research Institute, Division of Hematology Oncology, New England Medical Center, Boston, Massachusetts 02111, USA
Biochemistry 38:4572-85. 1999..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...
New tricks for old dogs: nonthrombotic effects of thrombin in vessel wall biologyC Patterson
Program in Molecular Cardiology and Department of Medicine, Lineberger Comprehensive Cancer Center and Center for Thrombosis, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7075, USA
Circ Res 88:987-97. 2001..In this review, we examine the activation of protease-activated receptors by thrombin, the downstream signaling events mediated by these receptors, and the physiological role of thrombin in vascular cells and vascular disease...
Human corneal epithelial cells express functional PAR-1 and PAR-2Roland Lang
Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia, USA
Invest Ophthalmol Vis Sci 44:99-105. 2003..The objective of this study was to examine whether HCECs express functional proteinase-activated receptor (PAR)-1 and -2 and evaluate the effects of receptor activation on corneal epithelial cell proinflammatory cytokine production...
Differential expression of protease-activated receptors 1, 2, and 4 on human endothelial cells from different vascular sitesMasakazu Fujiwara
Department of Molecular Pathology, Institute of Gerontology, Nippon Medical School, Kawasaki, Japan
Pathobiology 71:52-8. 2004..CONCLUSION: These findings suggest that each PAR preferentially targets an endothelial cell type, and thus plays a distinct role in diverse physiological or pathological conditions...
Macrophage migration inhibitory factor is induced by thrombin and factor Xa in endothelial cellsTadamichi Shimizu
Departments of Dermatology and Molecular Biochemistry, Hokkaido University Graduate School of Medicine, Sapporo 060 8638, Japan
J Biol Chem 279:13729-37. 2004..Taken together, these results suggest that MIF contributes to the inflammatory phase of the wound healing process in concert with thrombin and FXa via PAR-1 and PAR-2...
The agonist of the protease-activated receptor-1 (PAR) but not PAR3 mimics thrombin-induced vascular endothelial growth factor release in human smooth muscle cellsT Arisato
Department of Laboratory and Molecular Medicine, Faculty of Medicine, Kagoshima University, Kagoshima, Japan
Cell Mol Life Sci 60:1716-24. 2003..Thus, our data show that thrombin caused VEGF release via PARI activation in a manner dependent on [Ca2+]i and p44/42 downstream from the receptor activation...
Thrombin up-regulates tissue factor pathway inhibitor-2 synthesis through a cyclooxygenase-2-dependent, epidermal growth factor receptor-independent mechanismVeronique Neaud
Groupe de Recherches pour l Etude du Foie, INSERM E362 and IFR66, Universite Victor Segalen Bordeaux 2, 33076 Bordeaux, France
J Biol Chem 279:5200-6. 2004..The up-regulation of TFPI-2 expression by thrombin could in turn down-regulate thrombin generation and contribute to limit blood coagulation...
Inflammatory mediators modulate thrombin and cathepsin-G signaling in human bronchial fibroblasts by inducing expression of proteinase-activated receptor-4Rithwik Ramachandran
Division of Cardiovascular and Respiratory Studies, Postgraduate Medical Institute of the University of Hull, Hull York Medical Schoo, East Yorkshire, UK
Am J Physiol Lung Cell Mol Physiol 292:L788-98. 2007..These findings point to an important mechanism, whereby cellular responses to thrombin and cathepsin-G can be modified during an inflammatory response...
Role of protease-activated receptors in the vascular systemKatsuya Hirano
Division of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
J Atheroscler Thromb 10:211-25. 2003..Understanding the functional role of PARs in the vascular system can thus help in the development of new strategies for the prevention and therapy of vascular diseases...
Thrombin-stimulated growth, clustering, and collagen lattice contraction of human gingival fibroblasts is associated with its protease activityM C Chang
Team of Biomedical Science, Chang-Gung Institute of Nursing, Taoyuan, Taiwan
J Periodontol 72:303-13. 2001..The stimulatory effects of thrombin are associated with its protease activation of thrombin receptors...
alpha-Thrombin stimulates contraction of human bronchial rings by activation of protease-activated receptorsR W Hauck
Pneumologie der 1 Medizinischen Klinik und Deutsches Herzzentrum, Technische Universitat, 81675 Munich, Germany
Am J Physiol 277:L22-9. 1999..Further studies are needed to determine whether alpha-thrombin plays a role in stimulating bronchoconstriction in inflammatory airway diseases such as asthma and bronchiolitis obliterans...
Fibrin sealant promotes migration and proliferation of human articular chondrocytes: possible involvement of thrombin and protease-activated receptorsYaowanuj Kirilak
School of Surgery and Pathology (Orthopaedics, The University of Western Australia, Crawley WA 6009, Australia
Int J Mol Med 17:551-8. 2006..Together, these data demonstrate that FS supports both the migration and proliferation of human chondrocytes. We propose that these effects are mediated, at least in part, via thrombin-induced PAR-1 signalling in human chondrocytes...
Effects of inhaled thrombin receptor agonists in miceJames D Moffatt
Sackler Institute of Pulmonary Pharmacology, GKT School of Biomedical Sciences, Kings College London, 5th Floor Hodgkin Building, Guy s Campus, London SE1 9RT
Br J Pharmacol 143:269-75. 2004..In conclusion, exogenous thrombin has only a modest acute inflammatory action in the lung that appears to be mediated by PAR(4) and involve release of TNF-alpha from an unknown source...
Thrombin-stimulated proliferation of cultured human synovial fibroblasts through proteolytic activation of proteinase-activated receptor-1Ikue Furuhashi
Pharmacological Research Department, Research Laboratory, Minophagen Pharmaceutical Co Ltd, 2 2 3 Komatsubara, Zama, Kanagawa, Japan
J Pharmacol Sci 108:104-11. 2008....
Differential Ca(2+)responses induced by thrombin and thrombin-receptor agonist peptides in HSY-EA1 cellsAkihiko Tanimura
Department of Dental Pharmacology, School of Dentistry, Health Sciences University of Hokkaido, Ishikari Tobetsu, Hokkaido 061 0293, Japan
Cell Biol Int 27:1017-23. 2003..These observations indicate that thrombin disarms PAR-1 from further proteolytic activation, but leaves the receptor responsive for non-tethered ligands...
Proteolysis of the exodomain of recombinant protease-activated receptors: prediction of receptor activation or inactivation by MALDI mass spectrometryD Loew
Laboratoire de Spectrometrie de Masse Bio Organique, Universite Louis Pasteur, Strasbourg, France
Biochemistry 39:10812-22. 2000..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...
The effects of stimulating protease-activated receptor-1 and -2 in A172 human glioblastomaT Okamoto
Department of Surgery I, Okayama University Medical School, Japan
J Neural Transm 108:125-40. 2001..The uni-directional cross desensitization implies a functional linkage between PAR-1 and PAR-2 receptors...
Actin polymerisation regulates thrombin-evoked Ca(2+) signalling after activation of PAR-4 but not PAR-1 in human plateletsMatthew T Harper
Department of Physiology, University of Cambridge, Downing Street, Cambridge, UK
Platelets 17:134-42. 2006..These data suggest that Cyt D prevents the internalisation of PAR-4, which may lead to prolonged signalling from this receptor. This may mask a direct effect of Cyt D on the activation of SOCE after the activation of PAR-4...
Plasmin-mediated activation of platelets occurs by cleavage of protease-activated receptor 4Todd M Quinton
Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA
J Biol Chem 279:18434-9. 2004..Finally, a protease-resistant recombinant PAR-4 was refractory to activation by plasmin. We conclude that plasmin induces platelet aggregation primarily through slow cleavage of PAR-4...
Endothelial thrombomodulin induces Ca2+ signals and nitric oxide synthesis through epidermal growth factor receptor kinase and calmodulin kinase IIMonique David-Dufilho
Department of Signalisation Cellulaire et Atherosclerose Precoce, Universite Paris 6 CNRS, Paris 75014, France
J Biol Chem 280:35999-6006. 2005..This signaling may contribute to thrombomodulin function in thrombosis, inflammation, and atherosclerosis...
Thrombin receptors and protease-activated receptor-2 in human placentation: receptor activation mediates extravillous trophoblast invasion in vitroPeter J O'Brien
Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
Am J Pathol 163:1245-54. 2003..Together these results support a role for PAR1, and potentially PAR2 and PAR3 in the invasive phase of human placentation...
PARticipation in inflammationShaun R Coughlin
Cardiovascular Research Institute, University of California at San Francisco, San Francisco, California 94143, USA
J Clin Invest 111:25-7. 2003
Mechanisms of action of proteinase-activated receptor agonists on human plateletsAda W Y Chung
Department of Pharmacology, University of Alberta, Edmonton, Alberta, T6G 2H7, Canada
Br J Pharmacol 135:1123-32. 2002..11. Thus, the mechanisms of PAR1 and 4-induced platelet aggregation are distinct and depend differentially on their ability to interact with pathways of aggregation, along with the subsequent activation of GPIIb/IIIa receptors...
Protease-activated receptor-induced Akt activation--regulation and possible functionJ C Reséndiz
Wihuri Research Institute, Kalliolinnantie 4, Helsinki, Finland
J Thromb Haemost 5:2484-93. 2007..Akt activation is dependent on its phosphorylation at Thr308 and Ser473. The mechanism by which thrombin induces Akt phosphorylation is controversial, as is the role of Akt in platelet function...
Presence of functionally active protease-activated receptors 1 and 2 in myenteric gliaRosario Garrido
Department of Surgery, University of Michigan Medical Center, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0331, USA
J Neurochem 83:556-64. 2002....
[The role of PAR family receptors in activation of mast cells in the norm and in acute inflammation in rats]E V Kiseleva
M. V. Lomonossov State University, 119899, Vorobievy Gory, Moscow, Russia
Ross Fiziol Zh Im I M Sechenova 87:1527-33. 2001..Acceleration of the mast cell mediator secretion by the Xa factor and PAR-2 agonist, was revealed. An increase in the mast cell release induced by thrombin and TRAP-6 was shown in the acute peritonitis model...
Kinetic analysis of the cleavage of human protease-activated receptor-1 / 2 / 3 and 4 using quenched-fluorescent peptide substratesMark T Fox
Centre for Peptide and Protein Engineering, School of Biology and Biochemistry, Medical Biology Centre, The Queen s University of Belfast, 97, Lisburn Road, Belfast, BT9 7BL, Northern Ireland
Protein Pept Lett 9:387-97. 2002..Each substrate consisted of a ten-residue peptide spanning the receptor activation cleavage site and using progress-curve kinetics, k(cat) / K(m) values were determined...
Receptors of the PAR family as a link between blood coagulation and inflammationT N Dugina
Department of Human and Animal Physiology, School of Biology, Lomonosov Moscow State University, Moscow, 119899, Russia
Biochemistry (Mosc) 67:65-74. 2002..The presence of PAR receptors on mast cells is responsible for their reactivity to thrombin and factor Xa and defines their contribution to the association of inflammation and blood clotting processes...
Plasmin induces Cyr61 gene expression in fibroblasts via protease-activated receptor-1 and p44/42 mitogen-activated protein kinase-dependent signaling pathwayUsha R Pendurthi
Biomedical Research, The University of Texas Health Center at Tyler, Tex 75708, USA
Arterioscler Thromb Vasc Biol 22:1421-6. 2002..The aim of the present study was to elucidate potential mechanisms by which plasmin affects various cellular processes...
Participation of protease-activated receptor-1 in thrombin-induced microglial activationZhiming Suo
Neurobiology Research Laboratory, Veterans Affairs Medical Center, Kansas City, Missouri 64128, USA
J Neurochem 80:655-66. 2002..In addition, strategies aimed at blocking thrombin signaling through PAR1 may be therapeutically valuable for diseases associated with cerebral vascular damage and significant inflammation with microglial activation...
Role of protease-activated receptors in neutrophil degranulationS Kannan
Department of Physiology, School of Medicine, Temple University, Philadelphia, USA
Med Hypotheses 59:266-7. 2002..Based on the previous reports and supposition in perpetuity, it is hypothesized that thrombin through its receptor, and its subtypes, may very improbably have any functional role in PMN degranulation...
Protease-activated receptors upregulate cyclooxygenase-2 expression in human endothelial cellsRebecca A Houliston
Department of Veterinary Basic Sciences, Royal Veterinary College, University of London, Royal College Street, London, UK
Thromb Haemost 88:321-8. 2002..These results demonstrate that regulation of COX-2 induction is an important functional response of HUVEC to PAR activation and suggest that PARs promote sustained upregulation of prostanoid production in human endothelium...
Proteinase-activated receptor-1 (PAR(1)) and PAR(2) but not PAR(4) mediate contraction in human and guinea-pig gallbladdersM C Lee
Department of Surgery, Graduate Institute of Medicine, Tzu Chi University and Buddhist Tzu Chi General Hospital, Hualien, Taiwan
Neurogastroenterol Motil 20:385-91. 2008..PAR(1) and PAR(2) may play important roles in the control of both human and guinea-pig gallbladder motility...
Enzymatic activation of endothelial protease-activated receptors is dependent on artery diameter in human and porcine isolated coronary arteriesJustin R Hamilton
Department of Pharmacology, University of Melbourne, Victoria 3010, Australia
Br J Pharmacol 136:492-501. 2002....
Activation of endothelial cell protease activated receptor 1 by the protein C pathwayMatthias Riewald
Department of Immunology, C204, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA
Science 296:1880-2. 2002..Thus, the prototypical thrombin receptor is the target for EPCR-dependent APC signaling, suggesting a role for this receptor cascade in protection from sepsis...
Dual effect mediated by protease-activated receptors on the mechanical activity of rat colonFlavia Mulè
Dipartimento di Biologia Cellulare e dello Sviluppo, Universita di Palermo, Italy
Br J Pharmacol 136:367-74. 2002..PARs mediate changes of the mechanical activity of longitudinal and circular muscle which might explain the alterations of colonic motility observed during inflammatory conditions...
Four subtypes of protease-activated receptors, co-expressed in rat astrocytes, evoke different physiological signalingHong Wang
, , , Magdeburg, Germany
Glia 37:53-63. 2002....
Protease-activated receptor mediated RhoA signaling and cytoskeletal reorganization in LNCaP cellsDaniel L Greenberg
Department of Biochemistry, University of Washington, Box 357350, Seattle, Washington 98195 7350, USA
Biochemistry 42:702-9. 2003..Since the activation of RhoA is important for cytoskeletal reorganization, we postulate that PAR-mediated RhoA activation may be a major signaling pathway in the biology of prostate cancer...
Protease-activated receptor (PAR)-1 and PAR-2 participate in the cell growth of alveolar capillary endothelium in primary lung adenocarcinomasEnjing Jin
Department of Molecular Pathology, Institute of Gerontology, Nippon Medical School, Graduate School of Medicine, Kawasaki, Japan
Cancer 97:703-13. 2003..These results suggest a synergistic effect of PAR with vascular endothelial growth factor in alveolar angiogenesis...
Factor Xa and thrombin, but not factor VIIa, elicit specific cellular responses in dermal fibroblastsE B Bachli
Haemostasis Research, MRC Clinical Sciences Center, Faculty of Medicine, Imperial College, London, UK
J Thromb Haemost 1:1935-44. 2003..Tissue origin may influence the cellular response of fibroblasts to coagulation proteases...
Protease-activated receptors in the cardiovascular systemS R Coughlin
Cardiovascular Research Institute, Department of Medicine and Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California 94143, USA
Cold Spring Harb Symp Quant Biol 67:197-208. 2002
Differential expression and regulation of protease-activated receptors in human peripheral monocytes and monocyte-derived antigen-presenting cellsRenato Colognato
Department of Pharmacology of Natural Products and Clinical Pharmacology, University of Ulm, Germany
Blood 102:2645-52. 2003..These data demonstrate that differentiation of human monocytes is associated with differential expression of functionally active PARs that mediate distinct regulatory functions in inflammation and atherogenesis...
Research Grants
- Endothelial Myocyte Matrix in Cardiac RemodelingSURESH TYAGI; Fiscal Year: 2009....
- Endothelial Myocyte Matrix in Cardiac RemodelingSURESH TYAGI; Fiscal Year: 2009....
- Endothelial Myocyte Matrix in Cardiac RemodelingSuresh C Tyagi; Fiscal Year: 2010....
- THROMBIN RECEPTOR-G PROTEIN SIGNALING MECHANISMSAthan Kuliopulos; Fiscal Year: 2010....
- THROMBIN RECEPTOR-G PROTEIN SIGNALING MECHANISMSAthan Kuliopulos; Fiscal Year: 2007....
- Thrombin signaling and HIV dementiaKatherine Conant; Fiscal Year: 2006..abstract_text> ..
- Endothelial Dysfunction in Intestinal Radiation ToxicityMartin Hauer Jensen; Fiscal Year: 2007..This project may thus facilitate development of specific strategies to minimize intestinal radiation toxicity, thereby making radiation therapy safer and more effective. ..
- Endothelial Dysfunction in Intestinal Radiation ToxicityMartin Hauer Jensen; Fiscal Year: 2009..This project may thus facilitate development of specific strategies to minimize intestinal radiation toxicity, thereby making radiation therapy safer and more effective. ..
- G-protein-induced Signaling of PMN-mediated Lung InjuryArshad Rahman; Fiscal Year: 2005....
- TF Signaling in Systemic InflammationWolfram Ruf; Fiscal Year: 2010....
- Functional Cooperation of Tissue Factor and IntegrinsWolfram Ruf; Fiscal Year: 2010..Because a prototypic inhibitor of this pathway is effective to attenuate tumor growth in preclinical models, the proposed basic mechanistic studies facilitate a rational translation of this novel concept into the clinic. ..
- TARGETING SIGNALING OF THE TISSUE FACTOR PATHWAYWolfram Ruf; Fiscal Year: 2007..abstract_text> ..
- NEW GENETIC MODELS FOR TISSUE FACTOR SIGNALINGWolfram Ruf; Fiscal Year: 2007..Identification of such markers will facilitate the quantitation of coagulation signaling in vivo and thus advance clinical efforts to design therapeutic intervention in coagulant cell signaling pathways . ..
- Functional Cooperation of Tissue Factor and IntegrinsWolfram Ruf; Fiscal Year: 2007..Together, these experiments will characterize a novel pathway of integrin cooperation with TF of relevance for endothelial cell migration. ..
- PAR SIGNALING AND PROTECTIVE PATHWAYS IN INFLAMMATION AND SEPSISWolfram Ruf; Fiscal Year: 2010..3. ..
- ALLOSTERIC REGULATION OF FACTOR VII FUNCTIONWolfram Ruf; Fiscal Year: 2002..The detailed insight into allosteric regulation and determinants of substrate specificity in VIIa may provide novel strategies for therapeutic intervention in inflammatory and thrombotic diseases. ..
- SIGNALING OF TISSUE FACTOR IN CELL ADHESIONWolfram Ruf; Fiscal Year: 2001..In the long term, elucidation of the molecular details of TF signaling will guide novel therapeutic approaches that intervene with functions of TF in metastasis and angiogenesis. ..
- Structural Basis of Protease Signaling by VllaWolfram Ruf; Fiscal Year: 2003..abstract_text> ..
- LPS-PEPTIDE INTERACTION IN BLADDER INFLAMMATIONRicardo Saban; Fiscal Year: 2007..Information generated by this study should elucidate whether bladder inflammatory responses, regardless of etiology, occur via a common mechanism or whether the endpoints are specific for each stimulus. ..
- Urothelial Cell Physiology in Normal and Disease StatesRicardo Saban; Fiscal Year: 2005..Scott-Hultgren (Washington U) will discuss the molecular basis of persistent bladder infections. The bladder cancer discussion will be chaired by Drs. Robert Hurst (Oklahoma U) and Jenny Southgate (U. York). ..
- Thrombin,Sepsis and Mechanisms of InflammationChinnaswamy Tiruppathi; Fiscal Year: 2007..It is hoped that this work will lead to the development of new drug targeting acute lung injury associated with leaky lung microvessel and tissue edema formation. ..
- THROMBIN, SEPSIS AND MECHANISMS OF INFLAMMATIONChinnaswamy Tiruppathi; Fiscal Year: 2006..abstract_text> ..
- Thrombin,Sepsis and Mechanisms of InflammationChinnaswamy Tiruppathi; Fiscal Year: 2009..It is hoped that this work will lead to the development of new drug targeting acute lung injury associated with leaky lung microvessel and tissue edema formation. ..
- Bladder transcriptome in experimental inflammationRicardo Saban; Fiscal Year: 2007..Following target validation of SSH-selected genes, a custom array will be developed. This micro array will be used to determine how the bladder transcriptome is altered by BCG therapy. ..
- LPS-PEPTIDE INTERACTION IN BLADDER INFLAMMATIONRicardo Saban; Fiscal Year: 2006..Information generated by this study should elucidate whether bladder inflammatory responses, regardless of etiology, occur via a common mechanism or whether the endpoints are specific for each stimulus. ..
- LPS-PEPTIDE INTERACTION IN BLADDER INFLAMMATIONRicardo Saban; Fiscal Year: 2001..These studies will identify and define the important mechanisms involved in bladder inflammation and provide new insights for developing treatment strategies for cystitis. ..
- LPS-PEPTIDE INTERACTION IN BLADDER INFLAMMATIONRicardo Saban; Fiscal Year: 2003..These studies will identify and define the important mechanisms involved in bladder inflammation and provide new insights for developing treatment strategies for cystitis. ..
- LPS-PEPTIDE INTERACTION IN BLADDER INFLAMMATIONRicardo Saban; Fiscal Year: 2003..Information generated by this study should elucidate whether bladder inflammatory responses, regardless of etiology, occur via a common mechanism or whether the endpoints are specific for each stimulus. ..
- CELL RECEPTORS IN COAGULATION AND ATHEROGENESISSALVATORE PIZZO; Fiscal Year: 1991..These studies were undertaken since cis-DDP is an important antitumor drug which possesses two amine groups. It was felt that cis-DDP might react with alpha 2-M in a manner analogous to MeNH2...
- MOLECULAR BASIS OF COAGULATION PROTEASE SPECIFICITYALIREZA REZAIE; Fiscal Year: 2009....
- Diabetes, Inflammation and Vascular DiseaseSusan Smyth; Fiscal Year: 2004..Moreover, our results may have broad implications for the treatment and prevent of accelerated atherosclerosis and thrombosis in diabetes. ..
- CHRONIC HYPOXIA AND RESISTANCE TO MYOCARDIAL ISCHEMIAJohn Baker; Fiscal Year: 2007..The results of these studies are expected to have an impact on our understanding of the biology of Tpo in heart and may lead to the development of new therapeutics for the treatment of myocardial infarction. ..
- Modulation of Angiogenesis Via the Angiostatin ReceptorSALVATORE PIZZO; Fiscal Year: 2005..Because of the exposed intravascular localization of the ATP synthesizing enzymes, this project will yield a collection of anti-angiogenic compounds with strong potential for rapid translation into clinical studies. ..
- Lysolipid Signaling in Cardiovascular DiseaseSusan S Smyth; Fiscal Year: 2010..Completion of the work will provide new insights into pathways that could be targeted to prevent and treat arterial thrombosis. ..
- Lysolipid Signaling in Cardovascular DiseaseSusan Smyth; Fiscal Year: 2007..Our results will provide specific insights into the role of LPA signaling pathways in vascular physiology and pathology and may provide novels targets for the treatment and prevention of atherothrombotic disorders. ..
