par 1 receptor

Summary

Summary: 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

  1. ncbi Proteinase-activated receptors
    S R Macfarlane
    Department of Physiology and Pharmacology, University of Strathclyde, Strathclyde Institute for Biomedical Sciences, Glasgow, United Kingdom
    Pharmacol Rev 53:245-82. 2001
  2. ncbi PAR1 is a matrix metalloprotease-1 receptor that promotes invasion and tumorigenesis of breast cancer cells
    Adrienne Boire
    Molecular Oncology Research Institute, Tufts New England Medical Center, Boston, Massachusetts 02111, USA
    Cell 120:303-13. 2005
  3. pmc Protease-activated receptor-3 (PAR3) regulates PAR1 signaling by receptor dimerization
    Joseph 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
  4. pmc Matrix metalloproteinase-1 and thrombin differentially activate gene expression in endothelial cells via PAR-1 and promote angiogenesis
    Jessica S Blackburn
    Department of Biochemistry, Dartmouth Medical School, Lebanon, NH 03756, USA
    Am J Pathol 173:1736-46. 2008
  5. ncbi Protease-activated receptors in human airways: upregulation of PAR-2 in respiratory epithelium from patients with asthma
    D A Knight
    Asthma and Allergy Research Institute Inc, Nedlands, Western Australia, Australia
    J Allergy Clin Immunol 108:797-803. 2001
  6. pmc Absence of proteinase-activated receptor-1 signaling affords protection from bleomycin-induced lung inflammation and fibrosis
    David 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
  7. ncbi Thrombin responses in human endothelial cells. Contributions from receptors other than PAR1 include the transactivation of PAR2 by thrombin-cleaved PAR1
    P J O'Brien
    Departments of Medicine and Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    J Biol Chem 275:13502-9. 2000
  8. pmc An essential role for SNX1 in lysosomal sorting of protease-activated receptor-1: evidence for retromer-, Hrs-, and Tsg101-independent functions of sorting nexins
    Anuradha Gullapalli
    Department of Pharmacology, University of North Carolina at Chapel Hill, NC 27599 7365, USA
    Mol Biol Cell 17:1228-38. 2006
  9. pmc 'Role reversal' for the receptor PAR1 in sepsis-induced vascular damage
    Nicole 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
  10. pmc Protease-activated receptor 1 mediates thrombin-dependent, cell-mediated renal inflammation in crescentic glomerulonephritis
    M A Cunningham
    Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, 3168 Victoria, Australia
    J Exp Med 191:455-62. 2000

Detail Information

Publications198 found, 100 shown here

  1. ncbi Proteinase-activated receptors
    S 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...
  2. ncbi PAR1 is a matrix metalloprotease-1 receptor that promotes invasion and tumorigenesis of breast cancer cells
    Adrienne 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...
  3. pmc Protease-activated receptor-3 (PAR3) regulates PAR1 signaling by receptor dimerization
    Joseph 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...
  4. pmc Matrix metalloproteinase-1 and thrombin differentially activate gene expression in endothelial cells via PAR-1 and promote angiogenesis
    Jessica S Blackburn
    Department of Biochemistry, Dartmouth Medical School, Lebanon, NH 03756, USA
    Am J Pathol 173:1736-46. 2008
    ....
  5. ncbi Protease-activated receptors in human airways: upregulation of PAR-2 in respiratory epithelium from patients with asthma
    D A Knight
    Asthma and Allergy Research Institute Inc, Nedlands, Western Australia, Australia
    J Allergy Clin Immunol 108:797-803. 2001
    ..PARs are activated by endogenous proteases, including thrombin (PAR-1, -3, and -4) and tryptase (PAR-2 and -4), both of which are present in inflamed airways...
  6. pmc Absence of proteinase-activated receptor-1 signaling affords protection from bleomycin-induced lung inflammation and fibrosis
    David 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
    ....
  7. ncbi Thrombin responses in human endothelial cells. Contributions from receptors other than PAR1 include the transactivation of PAR2 by thrombin-cleaved PAR1
    P 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...
  8. pmc An essential role for SNX1 in lysosomal sorting of protease-activated receptor-1: evidence for retromer-, Hrs-, and Tsg101-independent functions of sorting nexins
    Anuradha 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...
  9. pmc 'Role reversal' for the receptor PAR1 in sepsis-induced vascular damage
    Nicole 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...
  10. pmc Protease-activated receptor 1 mediates thrombin-dependent, cell-mediated renal inflammation in crescentic glomerulonephritis
    M 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...
  11. pmc Persistent signaling by dysregulated thrombin receptor trafficking promotes breast carcinoma cell invasion
    Michelle A Booden
    Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7295, USA
    Mol Cell Biol 24:1990-9. 2004
    ..Thus, our results reveal that a novel alteration in trafficking of activated PAR1 causes persistent signaling and, in addition to other processes and proteins, contributes to breast carcinoma cell invasion...
  12. pmc Cysteinyl leukotriene 2 receptor and protease-activated receptor 1 activate strongly correlated early genes in human endothelial cells
    Barbara 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...
  13. ncbi Genetic evidence that protease-activated receptors mediate factor Xa signaling in endothelial cells
    Eric 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...
  14. ncbi Galpha(q) and Gbetagamma regulate PAR-1 signaling of thrombin-induced NF-kappaB activation and ICAM-1 transcription in endothelial cells
    Arshad 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...
  15. ncbi Plasmin desensitization of the PAR1 thrombin receptor: kinetics, sites of truncation, and implications for thrombolytic therapy
    A 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...
  16. ncbi Protease-activated receptor (PAR) 1 but not PAR2 or PAR4 mediates endothelium-dependent relaxation to thrombin and trypsin in human pulmonary arteries
    J 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...
  17. pmc Tethered ligand-derived peptides of proteinase-activated receptor 3 (PAR3) activate PAR1 and PAR2 in Jurkat T cells
    Kristina K Hansen
    Department of Pharmacology and Therapeutics, University of Calgary Faculty of Medicine, Calgary, Alberta, Canada
    Immunology 112:183-90. 2004
    ....
  18. ncbi Termination of protease-activated receptor-1 signaling by beta-arrestins is independent of receptor phosphorylation
    Chii 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...
  19. ncbi Review article: proteinase-activated receptors - novel signals for gastrointestinal pathophysiology
    N 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...
  20. ncbi Human corneal epithelial cells express functional PAR-1 and PAR-2
    Roland 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...
  21. ncbi Regulated shedding of PAR1 N-terminal exodomain from endothelial cells
    Matthew 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...
  22. ncbi Endothelial barrier protection by activated protein C through PAR1-dependent sphingosine 1-phosphate receptor-1 crossactivation
    Clemens Feistritzer
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Blood 105:3178-84. 2005
    ....
  23. ncbi Reaction of mast cell proteases tryptase and chymase with protease activated receptors (PARs) on keratinocytes and fibroblasts
    N 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...
  24. ncbi Protease-activated receptors: the role of cell-surface proteolysis in signalling
    Graeme 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...
  25. ncbi Activation of protease-activated receptor (PAR)-1, PAR-2, and PAR-4 stimulates IL-6, IL-8, and prostaglandin E2 release from human respiratory epithelial cells
    Nithiananthan 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...
  26. pmc The contribution of protease-activated receptor 1 to neuronal damage caused by transient focal cerebral ischemia
    Candice E Junge
    Department of Pharmacology, Emory University, Atlanta, GA 30322, USA
    Proc Natl Acad Sci U S A 100:13019-24. 2003
    ....
  27. ncbi The cytoprotective protein C pathway
    Laurent 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
    ....
  28. ncbi Signaling from protease-activated receptor-1 inhibits migration and invasion of breast cancer cells
    L Kamath
    Division of Hematology/Oncology, Molecular Cardiology Research Institute, New England Medical Center, Tufts University School of Medicine, Boston, MA 02111, USA
    Cancer Res 61:5933-40. 2001
    ..These findings suggest that therapeutics targeted toward G(i)-couplers that are selectively expressed in breast cancer cells could prove beneficial in halting the progression of invasive breast cancer...
  29. ncbi Protease-activated receptors (PAR1 and PAR2) contribute to tumor cell motility and metastasis
    Xiaoli Shi
    Cancer Biology Division, La Jolla Institute for Molecular Medicine, 4570 Executive Drive, San Diego, CA 92121, USA
    Mol Cancer Res 2:395-402. 2004
    ..Together, these data confirm a role for PAR1 in migration and metastasis and demonstrate an unexpected role for PAR2 in thrombin-dependent tumor cell migration and in metastasis...
  30. ncbi beta -Arrestins regulate protease-activated receptor-1 desensitization but not internalization or Down-regulation
    May M Paing
    Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, North Carolina 27599 7365, USA
    J Biol Chem 277:1292-300. 2002
    ....
  31. pmc Clathrin adaptor AP2 regulates thrombin receptor constitutive internalization and endothelial cell resensitization
    May 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...
  32. ncbi Thrombin receptor expression is upregulated in prostate cancer
    Varsha Kaushal
    Department of Internal Medicine, University of Arkansas for Medical Sciences, and Division of Hematology Oncology, Central Arkansas Veterans Healthcare System, Little Rock, Arkansas 72205, USA
    Prostate 66:273-82. 2006
    ..Aberrant expression of protease-activated receptors (PARs) has been associated with increased angiogenesis, tumor growth, and metastasis of various cancers. We assessed the status of PAR1 expression in prostate cancer...
  33. ncbi Expression of protease-activated receptors 1 and 2 in melanocytic nevi and malignant melanoma
    Daniela Massi
    Department of Human Pathology and Oncology, University of Florence, Florence, Italy
    Hum Pathol 36:676-85. 2005
    ..Conversely, the significance of PAR-2 up-regulation in both benign and malignant melanocytic lesions requires further research...
  34. ncbi Cdc42 regulates the restoration of endothelial barrier function
    Panos Kouklis
    Department of Pharmacology, University of Illinois College of Medicine, Chicago, Ill, USA
    Circ Res 94:159-66. 2004
    ..The delayed activation of Cdc42 represents a negative-feedback mechanism that signals AJ reassembly after the increase in endothelial permeability induced by inflammatory mediators such as thrombin...
  35. ncbi The pattern of expression of protease-activated receptors (PARs) during early trophoblast development
    Sharona 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...
  36. pmc Targeting melanoma growth and metastasis with systemic delivery of liposome-incorporated protease-activated receptor-1 small interfering RNA
    Gabriel J Villares
    Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA
    Cancer Res 68:9078-86. 2008
    ..We propose that siRNA incorporated into DOPC nanoparticles could be delivered systemically and used as a new modality for melanoma treatment...
  37. ncbi Role and regulation of the thrombin receptor (PAR-1) in human melanoma
    Carmen Tellez
    Department of Cancer Biology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Oncogene 22:3130-7. 2003
    ....
  38. ncbi The agonist of the protease-activated receptor-1 (PAR) but not PAR3 mimics thrombin-induced vascular endothelial growth factor release in human smooth muscle cells
    T 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...
  39. pmc Targeting a metalloprotease-PAR1 signaling system with cell-penetrating pepducins inhibits angiogenesis, ascites, and progression of ovarian cancer
    Anika Agarwal
    Molecular Oncology Research Institute, Tufts Medical Center, Box 7510, Boston, MA 02111, USA
    Mol Cancer Ther 7:2746-57. 2008
    ..These data provide an in vivo proof-of-concept that targeting the metalloprotease-PAR1 signaling system may be a novel therapeutic approach in the treatment of ovarian cancer...
  40. ncbi The thrombin receptor, PAR-1, causes transformation by activation of Rho-mediated signaling pathways
    C B Martin
    Department of Pharmacology and Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina NC 27599-7295, USA
    Oncogene 20:1953-63. 2001
    ..Taken together, these observations suggest that PAR-1 growth transformation is mediated, in part, by activation of RhoA...
  41. ncbi PAR1 cleavage and signaling in response to activated protein C and thrombin
    Matthew J Ludeman
    Cardiovascular Research Institute, University of California, San Francisco, California 94143 0130, USA
    J Biol Chem 280:13122-8. 2005
    ..Although consistent with reports that sufficiently high concentrations of APC can cleave and activate PAR1 in culture, our data suggest that a significant physiological role for PAR1 activation by APC is unlikely...
  42. ncbi Thrombin/thrombin receptor (PAR-1)-mediated induction of IL-8 and VEGF expression in prostate cancer cells
    Jian 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...
  43. pmc Persistent transactivation of EGFR and ErbB2/HER2 by protease-activated receptor-1 promotes breast carcinoma cell invasion
    P 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...
  44. ncbi Interleukin-6 production by endothelial cells via stimulation of protease-activated receptors is amplified by endotoxin and tumor necrosis factor-alpha
    L 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...
  45. ncbi PAR1 thrombin receptor-G protein interactions. Separation of binding and coupling determinants in the galpha subunit
    S Swift
    Molecular Cardiology Research Institute, Division of Hematology, New England Medical Center, Boston, Massachusetts 02111, USA
    J Biol Chem 275:2627-35. 2000
    ....
  46. pmc Unproductive cleavage and the inactivation of protease-activated receptor-1 by trypsin in vascular endothelial cells
    Tetsuzo 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...
  47. ncbi A role for thrombin receptor signaling in endothelial cells during embryonic development
    C T Griffin
    Cardiovascular Research Institute, University of California at San Francisco UCSF, San Francisco, California 94143
    Science 293:1666-70. 2001
    ....
  48. ncbi Functional selectivity of G protein signaling by agonist peptides and thrombin for the protease-activated receptor-1
    Joseph 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...
  49. pmc Differential expression of protease-activated receptors-1 and -2 in stromal fibroblasts of normal, benign, and malignant human tissues
    M 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...
  50. ncbi Protease-activated receptors 1 and 4 mediate thrombin signaling in endothelial cells
    Hiroshi 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...
  51. pmc Expression of protease-activated receptor-1, -2, -3, and -4 in control and experimentally inflamed mouse bladder
    Michael 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...
  52. ncbi Amplification of MMP-2 and MMP-9 production by prostate cancer cell lines via activation of protease-activated receptors
    Susan R Wilson
    School of Pharmacy, Medical Biology Centre, Queens University Belfast, 97 Lisburn Road, Belfast, United Kingdom
    Prostate 60:168-74. 2004
    ..Protease-activated receptors (PARs) have previously been shown to be involved in pathways of MMP upregulation by tumor cells...
  53. pmc Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin
    M 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...
  54. ncbi Human protease-activated receptor 1 expression in malignant epithelia: a role in invasiveness
    Yong 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...
  55. pmc Distinct roles of protease-activated receptors in signal transduction regulation of endothelial nitric oxide synthase
    Hiroyuki 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
    ....
  56. ncbi Extracellular mediators in atherosclerosis and thrombosis: lessons from thrombin receptor knockout mice
    Christopher 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
    ....
  57. ncbi 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...
  58. ncbi Role of the PAR1 receptor 8th helix in signaling: the 7-8-1 receptor activation mechanism
    Steven 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...
  59. ncbi Protease-activated receptor stimulation activates a Ca2+-independent phospholipase A2 in bladder microvascular endothelial cells
    Alice 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
    ....
  60. pmc A role for proteinase-activated receptor-1 in inflammatory bowel diseases
    Nathalie Vergnolle
    Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, Canada
    J Clin Invest 114:1444-56. 2004
    ....
  61. ncbi Tumor cell invasion is promoted by activation of protease activated receptor-1 in cooperation with the alpha vbeta 5 integrin
    S 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...
  62. ncbi Thrombin induces endocytosis of endoglin and type-II TGF-beta receptor and down-regulation of TGF-beta signaling in endothelial cells
    Hua 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...
  63. pmc Activation of sphingosine kinase-1 reverses the increase in lung vascular permeability through sphingosine-1-phosphate receptor signaling in endothelial cells
    Mohammad 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...
  64. pmc Agonists of proteinase-activated receptor 1 induce plasma extravasation by a neurogenic mechanism
    L 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...
  65. ncbi Characterization and functional activity of thrombin receptors in the human lens
    Colin James
    School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK
    Invest Ophthalmol Vis Sci 46:925-32. 2005
    ..To investigate the expression of thrombin receptors in the human lens, the activation of downstream signaling pathways, and the ability of thrombin to regulate lens cell growth...
  66. ncbi Protease-activated receptor-1 (hPar1), a survival factor eliciting tumor progression
    Zaidoun 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...
  67. ncbi Activated protein C blocks p53-mediated apoptosis in ischemic human brain endothelium and is neuroprotective
    Tong 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...
  68. ncbi Protease-activated receptors in inflammation, neuronal signaling and pain
    N 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...
  69. ncbi Protease-activated receptor 1: a role in prostate cancer metastasis
    Ta Chun Yuan
    Department of Biochemistry, University of Nebraska Medical Center, Omaha, NE 68198 5870, USA
    Clin Prostate Cancer 3:189-91. 2004
    ....
  70. ncbi A tyrosine-based sorting signal regulates intracellular trafficking of protease-activated receptor-1: multiple regulatory mechanisms for agonist-induced G protein-coupled receptor internalization
    May 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...
  71. pmc Activation and inhibition of G protein-coupled receptors by cell-penetrating membrane-tethered peptides
    Lidija 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...
  72. ncbi Phospholipid metabolite production in human urothelial cells after protease-activated receptor cleavage
    Alice 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...
  73. ncbi Differential expression of protease activated receptor 1 (Par1) and pY397FAK in benign and malignant human ovarian tissue samples
    Sorina 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...
  74. ncbi von Hippel-Lindau tumor suppressor protein stimulation by thrombin involves RhoA activation
    Sandra Turcotte
    Laboratoire de Medecine Moleculaire, Hopital Sainte Justine, Universite du Quebec a Montreal, Montreal, Quebec
    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...
  75. pmc Thrombin induces fibroblast CCL2/JE production and release via coupling of PAR1 to Galphaq and cooperation between ERK1/2 and Rho kinase signaling pathways
    Xiaoling Deng
    Centre for Respiratory Research, University College London, London WC1E 6JJ, United Kingdom
    Mol Biol Cell 19:2520-33. 2008
    ....
  76. ncbi New tricks for old dogs: nonthrombotic effects of thrombin in vessel wall biology
    C 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...
  77. ncbi Abrogation of thrombin-induced increase in pulmonary microvascular permeability in PAR-1 knockout mice
    S 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...
  78. pmc How the protease thrombin talks to cells
    S 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...
  79. ncbi Effect of human airway trypsin-like protease on intracellular free Ca2+ concentration in human bronchial epithelial cells
    Mari Miki
    Department of Internal Medicine and Molecular Therapeutics, The University of Tokushima School of Medicine, Tokushima, Japan
    J Med Invest 50:95-107. 2003
    ..The Ca2+ response to HAT was desensitized by exposure of HBEC to PAR-2 AP. These results indicate that HBEC have a functional PAR-2, and HAT regulates cellular functions of HBEC via activation of PAR-2...
  80. ncbi Protease-activated receptor-2 is essential for factor VIIa and Xa-induced signaling, migration, and invasion of breast cancer cells
    Dionne 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
    ....
  81. ncbi Protease-activated receptors upregulate cyclooxygenase-2 expression in human endothelial cells
    Rebecca 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...
  82. ncbi Receptors of the PAR family as a link between blood coagulation and inflammation
    T 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...
  83. ncbi Participation of protease-activated receptor-1 in thrombin-induced microglial activation
    Zhiming 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...
  84. pmc Mechanisms of action of proteinase-activated receptor agonists on human platelets
    Ada 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...
  85. ncbi Protease-activated receptors 1 and 4 do not stimulate G(i) signaling pathways in the absence of secreted ADP and cause human platelet aggregation independently of G(i) signaling
    Soochong Kim
    Department of Physiology and the Sol Sherry Thrombosis Research Center, Temple University School of Medicine, Philadelphia, PA 19140, USA
    Blood 99:3629-36. 2002
    ....
  86. ncbi alpha-Thrombin stimulates contraction of human bronchial rings by activation of protease-activated receptors
    R 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...
  87. pmc Dual effect mediated by protease-activated receptors on the mechanical activity of rat colon
    Flavia 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...
  88. ncbi Activation of endothelial cell protease activated receptor 1 by the protein C pathway
    Matthias 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...
  89. pmc Enzymatic activation of endothelial protease-activated receptors is dependent on artery diameter in human and porcine isolated coronary arteries
    Justin R Hamilton
    Department of Pharmacology, University of Melbourne, Victoria 3010, Australia
    Br J Pharmacol 136:492-501. 2002
    ....
  90. ncbi Inflammatory mediators modulate thrombin and cathepsin-G signaling in human bronchial fibroblasts by inducing expression of proteinase-activated receptor-4
    Rithwik 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...
  91. pmc Effects of inhaled thrombin receptor agonists in mice
    James 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...
  92. ncbi [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...
  93. ncbi Actin polymerisation regulates thrombin-evoked Ca(2+) signalling after activation of PAR-4 but not PAR-1 in human platelets
    Matthew 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...
  94. ncbi Endothelial thrombomodulin induces Ca2+ signals and nitric oxide synthesis through epidermal growth factor receptor kinase and calmodulin kinase II
    Monique 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...
  95. ncbi Fibrin sealant promotes migration and proliferation of human articular chondrocytes: possible involvement of thrombin and protease-activated receptors
    Yaowanuj 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...
  96. ncbi Proteolysis of the exodomain of recombinant protease-activated receptors: prediction of receptor activation or inactivation by MALDI mass spectrometry
    D 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...
  97. ncbi The effects of stimulating protease-activated receptor-1 and -2 in A172 human glioblastoma
    T 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...
  98. ncbi Thrombin-stimulated growth, clustering, and collagen lattice contraction of human gingival fibroblasts is associated with its protease activity
    M 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...
  99. pmc Proteinase-activated receptor-1 (PAR-1) activation contracts the isolated human renal artery in vitro
    Michele Tognetto
    Department of Experimental and Clinical Medicine, Pharmacology Unit, University of Ferrara, S Anna Hospital, via Fossato di Mortara 19, 44100 Ferrara, Italy
    Br J Pharmacol 139:21-7. 2003
    ..5. In agreement with the motor function data immunohistochemistry showed specific staining patterns for PAR-1 in the human renal artery. 6. Combined, these studies would suggest a possible role for PAR-1 in renal vascular homeostasis...
  100. pmc Mechanism of trypsin-induced contraction in the rat myometrium: the possible involvement of a novel member of protease-activated receptor
    Y Shintani
    Division of Molecular Cardiology, Research Institute of Angiocardiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan
    Br J Pharmacol 133:1276-85. 2001
    ..Trypsin was thus suggested to contract the rat myometrium via a novel type of PAR, which might be upregulated during pregnancy...
  101. ncbi Thrombin suppresses endothelial nitric oxide synthase and upregulates endothelin-converting enzyme-1 expression by distinct pathways: role of Rho/ROCK and mitogen-activated protein kinase
    M Eto
    Department of Cardiology, University Hospital, Institutes of Physiology, , Switzerland
    Circ Res 89:583-90. 2001
    ..These effects of thrombin may be important for endothelial dysfunction in cardiovascular disease, particularly during acute coronary episodes...

Research Grants49

  1. Screening for allosteric modulators of the protease activated receptor 4
    Heidi E Hamm; Fiscal Year: 2013
    ..These studies should provide valuable tool compounds which would have advantages of temporal and spatial specificity, becoming efficacious only when thrombin is present. ..
  2. Endothelial Myocyte Matrix in Cardiac Remodeling
    Suresh C Tyagi; Fiscal Year: 2013
    ..PHS 398/2590 (Rev. 11/07) Page Continuation Format Page ..
  3. Optimization of PAR4 antagonists for thrombotic disorders
    Heidi E Hamm; Fiscal Year: 2013
    ..These studies should provide a valuable tool compound which will enable studies that may reveal PAR4 as an alternative target for preventive and therapeutic suppression of pathologic thrombus formation. ..
  4. Mitophagic and anti-angiogenic mechanism of heart failure
    Suresh C Tyagi; Fiscal Year: 2013
    ..The positive outcome of this project will have therapeutic ramifications for chronic heart failure. ..
  5. Endothelial Dysfunction in Intestinal Radiation Toxicity
    Martin 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. ..
  6. TARGETING SIGNALING OF THE TISSUE FACTOR PATHWAY
    Wolfram Ruf; Fiscal Year: 2007
    ..abstract_text> ..
  7. PAR SIGNALING AND PROTECTIVE PATHWAYS IN INFLAMMATION AND SEPSIS
    Wolfram Ruf; Fiscal Year: 2010
    ..3. ..
  8. Thrombin,Sepsis and Mechanisms of Inflammation
    Chinnaswamy Tiruppathi; Fiscal Year: 2010
    ..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. ..
  9. Urothelial Cell Physiology in Normal and Disease States
    Ricardo 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). ..
  10. LPS-PEPTIDE INTERACTION IN BLADDER INFLAMMATION
    Ricardo 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. ..
  11. Bladder transcriptome in experimental inflammation
    Ricardo 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. ..
  12. PKD Family Kinases and Idiopathic Pulmonary Fibrosis
    Hua Tang; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable] [unreadable]..
  13. MMPs and Synaptic Injury with HIV/METH
    Katherine Conant; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  14. Role of Plasminogen in Apoptosis
    Jennifer Mitchell; Fiscal Year: 2005
    ..This hypothesis is based on preliminary results, which demonstrate that the addition of plasminogen to monocytes significantly impedes apoptosis. ..
  15. Myocyte signaling and the response to stress
    WINSTON PATTERSON; Fiscal Year: 2009
    ....
  16. Carolina Cardiopulmonary Gene Expression Services
    WINSTON PATTERSON; Fiscal Year: 2005
    ..abstract_text> ..
  17. Platelet Membrane Proteins in Thrombosis
    Susan Smyth; Fiscal Year: 2005
    ..This work will identify a novel target for future antithrombotic strategies and challenge the assumption that the beneficial effects of P-selectin antagonists are exclusive to leukocytes. ..
  18. MECHANISM OF HUMAN MAST CELL TRYPTASE REGULATION
    Norman Schechter; Fiscal Year: 2003
    ..Understanding the structural properties responsible for the functional instability may provide new targets for therapeutic inhibitors. ..
  19. Thrombin signaling and HIV dementia
    Katherine Conant; Fiscal Year: 2006
    ..abstract_text> ..
  20. The biology of Ron, the HGF-like protein receptor
    SANDRA DEGEN; Fiscal Year: 2004
    ....
  21. Tissue Factor-factor Vlla signaling
    Usha Pendurthi; Fiscal Year: 2010
    ..The proposed studies will provide valuable information in understanding how TF contributes to tumorigenesis. These studies will also provide clues on potential therapeutic targets for prevention of cancer progression. ..
  22. CHRONIC HYPOXIA AND RESISTANCE TO MYOCARDIAL ISCHEMIA
    John E Baker; Fiscal Year: 2010
    ..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. ..
  23. MOLECULAR BASIS OF COAGULATION PROTEASE SPECIFICITY
    Alireza R Rezaie; Fiscal Year: 2010
    ....
  24. Epithelial Innate Immune Response to Oral Bacteria
    WHASUN CHUNG; Fiscal Year: 2008
    ..This work will lay the groundwork for identifying new therapeutic targets to prevent and treat periodontal diseases. [unreadable] [unreadable]..
  25. REGULATION OF PLATELET SHAPE CHANGES
    John Hartwig; Fiscal Year: 2008
    ..abstract_text> ..
  26. Radiation injury to the heart
    John E Baker; Fiscal Year: 2010
    ..1 ..
  27. Mast Cell-Induced Inflammation in Vascular Disease
    Kottarappat N Dileepan; Fiscal Year: 2010
    ..abstract_text> ..
  28. Regulation of Beta-Defensin Expression in Oral Epithelia
    WHASUN CHUNG; Fiscal Year: 2009
    ..These studies will lead to new insights on the role of innate immunity and new potential targets for therapeutic drug development for oral infections. ..
  29. SERINE PROTEASES FROM MAST CELLS AND SKIN
    Norman Schechter; Fiscal Year: 2002
    ..It is hoped that these studies will advance our understanding of two classes of molecules which are important to production and regulation of inflammation. ..
  30. GENETICS AND INTERMITTENT MYOCARDIAL HYPOXIA
    John Baker; Fiscal Year: 2003
    ....
  31. Alpha2-Macroglobulin-PA Complexes: Novel Anthrax Vaccin*
    SALVATORE PIZZO; Fiscal Year: 2003
    ..These studies will provide a new anthrax vaccine candidate with both improved immunogenicity and decreased reactogenicity. ..
  32. Aging, Stress and Atherosclerosis
    WINSTON PATTERSON; Fiscal Year: 2003
    ..Based on these studies, we will create molecular portraits of the ROS-dependent and ROS-independent transcripts preferentially associated with aging. ..
  33. PROTEASE-ACTIVATED RECEPTOR ACTIONS IN CARDIOMYOCYTES
    Susan Steinberg; Fiscal Year: 2004
    ....
  34. HIV 1 PROTEINS AND DRUGS OF ABUSE AND METALLOPROTEASES
    Katherine Conant; Fiscal Year: 2003
    ..We will also examine the mechanisms by which these substances may affect MMP production, and identify clinically tolerable compounds which may inhibit such production. ..
  35. Tyrosine Phosphatases and Endothelial Dysfunction
    Hua Tang; Fiscal Year: 2004
    ..abstract_text> ..
  36. Molecular Mechanisms of PAR1 Downregulation
    JoAnn Trejo; Fiscal Year: 2005
    ..Thus we will use the C-tail of PAR1 as a probe in protein-protein interaction based strategies to identify new molecules that recognize and sort PAR1 to lysosomes...
  37. ACTIVATED ENDOTHELIAL ADHESIVITY IN SC VASOOCCLUSION
    Stephen Embury; Fiscal Year: 2003
    ..They may provide the basis for future therapeutic interventions. ..
  38. CELL RECEPTORS IN COAGULATION AND ATHEROGENESIS
    SALVATORE PIZZO; Fiscal Year: 2006
    ..Future studies will determine whether this pathway also is essential for alpha2M-antigen processing and presentation. ..
  39. Regulation of Human Beta-Defensins in Epithelia
    WHASUN CHUNG; Fiscal Year: 2006
    ..Identifying specific routes pathogens take in stimulating beta-defensins may open the way for development of new therapeutic agents that stimulate the innate immune response. ..
  40. MMPs in neural networking
    Katherine Conant; Fiscal Year: 2006
    ..The results of our studies should improve our understanding of those CNS inflammatory diseases that are characterized by elevated levels of MMPs. [unreadable] [unreadable] [unreadable]..
  41. PI3K in LPS-induced coagulation and inflammation
    James Luyendyk; Fiscal Year: 2006
    ..Ultimately, characterization of the involvement of this pathway in LPS-induced inflammation may allow for development of novel strategies that can be used to treat sepsis. [unreadable] [unreadable] [unreadable]..
  42. Localization and activation of protease receptor PAR1
    CANDICE JUNGE; Fiscal Year: 2002
    ..Because tPA is currently approved for stroke, these studies may lead to a possible adjunct therapy that enhances tPA?s beneficial effects. ..
  43. b1-/b2-Adrenergic Receptor Mechanisms in Cardiomyocytes
    Susan Steinberg; Fiscal Year: 2007
    ..As such, these studies are likely to suggest novel clinical strategies that might be pursued (or should be avoided) for the management of chronic heart failure in humans. ..
  44. MMPS IN HIV DEMENTIA: EFFECTS ON BBB STRUCTURE/FUNCTION
    Katherine Conant; Fiscal Year: 2003
    ..Also, the proposed studies will use both primary brain-derived HIV isolates, which differ from laboratory adapted strains, and normal human cells, which also differ significantly from those of rodent or tumor origin. ..
  45. Diabetes, Inflammation and Vascular Disease
    Susan Smyth; Fiscal Year: 2004
    ..Moreover, our results may have broad implications for the treatment and prevent of accelerated atherosclerosis and thrombosis in diabetes. ..
  46. Modulation of Angiogenesis Via the Angiostatin Receptor
    SALVATORE 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. ..
  47. Microglial Cell Activation by Thrombin in Stroke
    Jonathan Weinstein; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  48. Integrin Signaling In Vascular Cells
    Susan Smyth; Fiscal Year: 2009
    ..abstract_text> ..