PAR-1

Summary

Gene Symbol: PAR-1
Description: coagulation factor II thrombin receptor
Alias: CF2R, HTR, PAR-1, PAR1, proteinase-activated receptor 1, protease-activated receptor 1
Species: human
Products:     PAR-1

Top Publications

  1. Shi X, Gangadharan B, Brass L, Ruf W, Mueller B. Protease-activated receptors (PAR1 and PAR2) contribute to tumor cell motility and metastasis. Mol Cancer Res. 2004;2:395-402 pubmed
    ..thrombin on tumor cells are commonly thought to be mediated by the thrombin receptor protease-activated receptor 1 (PAR1)...
  2. Suzuki T, Yamashita C, Zemans R, Briones N, Van Linden A, Downey G. Leukocyte elastase induces lung epithelial apoptosis via a PAR-1-, NF-kappaB-, and p53-dependent pathway. Am J Respir Cell Mol Biol. 2009;41:742-55 pubmed publisher
    ..Further, p53 contributes to elastase-induced apoptosis by both transcriptional and post-transcriptional mechanisms. ..
  3. Tantivejkul K, Loberg R, Mawocha S, Day L, John L, Pienta B, et al. PAR1-mediated NFkappaB activation promotes survival of prostate cancer cells through a Bcl-xL-dependent mechanism. J Cell Biochem. 2005;96:641-52 pubmed
    We have previously reported that protease-activated receptor 1 (PAR1 or thrombin receptor) is over-expressed in metastatic prostate cancer cell lines compared to prostate epithelial cells...
  4. Gigante B, Vikström M, Meuzelaar L, Chernogubova E, Silveira A, Hooft F, et al. Variants in the coagulation factor 2 receptor (F2R) gene influence the risk of myocardial infarction in men through an interaction with interleukin 6 serum levels. Thromb Haemost. 2009;101:943-53 pubmed
    ..03). Our results demonstrate that in men F2R genetic variants influence the risk of MI mainly through an interaction with IL6 serum levels. ..
  5. Zigler M, Kamiya T, Brantley E, Villares G, Bar Eli M. PAR-1 and thrombin: the ties that bind the microenvironment to melanoma metastasis. Cancer Res. 2011;71:6561-6 pubmed publisher
    ..Inhibiting such interactions by targeting PAR-1 could potentially be a useful therapeutic modality for melanoma patients. ..
  6. Tellez C, Bar Eli M. Role and regulation of the thrombin receptor (PAR-1) in human melanoma. Oncogene. 2003;22:3130-7 pubmed
  7. Yin Y, Salah Z, Grisaru Granovsky S, Cohen I, Even Ram S, Maoz M, et al. Human protease-activated receptor 1 expression in malignant epithelia: a role in invasiveness. Arterioscler Thromb Vasc Biol. 2003;23:940-4 pubmed
    ..b>PAR1 expression correlates with the invasion properties of breast carcinoma, whereas human PAR1 antisense reduces their ..
  8. Dores M, Chen B, Lin H, Soh U, Paing M, Montagne W, et al. ALIX binds a YPX(3)L motif of the GPCR PAR1 and mediates ubiquitin-independent ESCRT-III/MVB sorting. J Cell Biol. 2012;197:407-19 pubmed publisher
    ..We previously showed that protease-activated receptor 1 (PAR1), a G protein-coupled receptor (GPCR) for thrombin, is internalized after activation and sorted to lysosomes ..
  9. Coughlin S. Protease-activated receptors in hemostasis, thrombosis and vascular biology. J Thromb Haemost. 2005;3:1800-14 pubmed

More Information

Publications73

  1. Even Ram S, Maoz M, Pokroy E, Reich R, Katz B, Gutwein P, et al. Tumor cell invasion is promoted by activation of protease activated receptor-1 in cooperation with the alpha vbeta 5 integrin. J Biol Chem. 2001;276:10952-62 pubmed
    The first prototype of the protease activated receptor (PAR) family, the thrombin receptor PAR1, plays a central role both in the malignant invasion process of breast carcinoma metastasis and in the physiological process of placental ..
  2. Gullapalli A, Wolfe B, Griffin C, Magnuson T, Trejo J. An essential role for SNX1 in lysosomal sorting of protease-activated receptor-1: evidence for retromer-, Hrs-, and Tsg101-independent functions of sorting nexins. Mol Biol Cell. 2006;17:1228-38 pubmed
    ..To assess SNX1 function in endocytic sorting of protease-activated receptor-1 (PAR1), we used siRNA to deplete HeLa cells of endogenous SNX1 protein...
  3. Even Ram S, Uziely B, Cohen P, Grisaru Granovsky S, Maoz M, Ginzburg Y, et al. Thrombin receptor overexpression in malignant and physiological invasion processes. Nat Med. 1998;4:909-14 pubmed
    ..These results emphasize the involvement of thrombin receptor in cell invasion associated with tumor progression and normal embryonic development. ..
  4. Melnikova V, Balasubramanian K, Villares G, Dobroff A, Zigler M, Wang H, et al. Crosstalk between protease-activated receptor 1 and platelet-activating factor receptor regulates melanoma cell adhesion molecule (MCAM/MUC18) expression and melanoma metastasis. J Biol Chem. 2009;284:28845-55 pubmed publisher
    ..Here, we demonstrate a novel signaling mechanism whereby protease-activated receptor 1 (PAR1) mediates expression of melanoma cell adhesion molecule MCAM/MUC18 (MUC18), a critical marker of melanoma ..
  5. Smith S, Judge H, Peters G, Armstrong M, Dupont A, Gaussem P, et al. PAR-1 genotype influences platelet aggregation and procoagulant responses in patients with coronary artery disease prior to and during clopidogrel therapy. Platelets. 2005;16:340-5 pubmed
    ..Higher platelet reactivity associated with PAR-1 IVSn-14 A allele homozygotes persists despite clopidogrel therapy. These individuals may be at higher risk of thromboembolic events and may require additional anti-platelet medication. ..
  6. Kaufmann R, Rahn S, Pollrich K, Hertel J, Dittmar Y, Hommann M, et al. Thrombin-mediated hepatocellular carcinoma cell migration: cooperative action via proteinase-activated receptors 1 and 4. J Cell Physiol. 2007;211:699-707 pubmed
    ..We suggest that a combined inhibition of coagulation cascade serine proteinases, the two PARs and their complex signaling pathways may provide a new strategy for treating hepatocellular carcinoma. ..
  7. Trivedi V, Boire A, Tchernychev B, Kaneider N, Leger A, O Callaghan K, et al. Platelet matrix metalloprotease-1 mediates thrombogenesis by activating PAR1 at a cryptic ligand site. Cell. 2009;137:332-43 pubmed publisher
    ..We show that platelet MMP-1 activates protease-activated receptor-1 (PAR1) on the surface of platelets...
  8. Xiao Y, Morice A, Compton S, Sadofsky L. N-linked glycosylation regulates human proteinase-activated receptor-1 cell surface expression and disarming via neutrophil proteinases and thermolysin. J Biol Chem. 2011;286:22991-3002 pubmed publisher
  9. Grisaru Granovsky S, Salah Z, Maoz M, Pruss D, Beller U, Bar Shavit R. Differential expression of protease activated receptor 1 (Par1) and pY397FAK in benign and malignant human ovarian tissue samples. Int J Cancer. 2005;113:372-8 pubmed
    ..In our present study we investigated the expression pattern of protease activated receptor 1 hPar1 in ovarian carcinoma tissue samples...
  10. Vu T, Hung D, Wheaton V, Coughlin S. Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell. 1991;64:1057-68 pubmed
    ..These data reveal a novel signaling mechanism in which thrombin cleaves its receptor's amino-terminal extension to create a new receptor amino terminus that functions as a tethered ligand and activates the receptor. ..
  11. Booden M, Eckert L, Der C, Trejo J. Persistent signaling by dysregulated thrombin receptor trafficking promotes breast carcinoma cell invasion. Mol Cell Biol. 2004;24:1990-9 pubmed
    Increased expression of protease-activated receptor 1 (PAR1), a G protein-coupled receptor for thrombin, has previously been correlated with breast carcinoma cell invasion...
  12. Shapiro M, Trejo J, Zeng D, Coughlin S. Role of the thrombin receptor's cytoplasmic tail in intracellular trafficking. Distinct determinants for agonist-triggered versus tonic internalization and intracellular localization. J Biol Chem. 1996;271:32874-80 pubmed
    ..They further suggest that maintenance of the intracellular pool of naive thrombin receptors requires tonic receptor internalization. ..
  13. Chambers R, Dabbagh K, McAnulty R, Gray A, Blanc Brude O, Laurent G. Thrombin stimulates fibroblast procollagen production via proteolytic activation of protease-activated receptor 1. Biochem J. 1998;333 ( Pt 1):121-7 pubmed
    ..These results suggest that thrombin might influence the deposition of connective tissue proteins during normal wound healing and the development of tissue fibrosis by stimulating fibroblast procollagen production. ..
  14. Asokananthan N, Graham P, Fink J, Knight D, Bakker A, McWilliam A, et al. 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. J Immunol. 2002;168:3577-85 pubmed
    ..Combined, these data suggest an important role for PAR in the modulation of inflammation in the lung. ..
  15. Loew D, Perrault C, Morales M, Moog S, Ravanat C, Schuhler S, et al. Proteolysis of the exodomain of recombinant protease-activated receptors: prediction of receptor activation or inactivation by MALDI mass spectrometry. Biochemistry. 2000;39:10812-22 pubmed
    ..Thrombin selectively cleaves PAR1, PAR3, and PAR4 to induce activation of platelets and vascular cells, while PAR2 is preferentially cleaved by ..
  16. Swift S, Leger A, Talavera J, Zhang L, Bohm A, Kuliopulos A. Role of the PAR1 receptor 8th helix in signaling: the 7-8-1 receptor activation mechanism. J Biol Chem. 2006;281:4109-16 pubmed
    ..The archetypic protease-activated receptor PAR1 strongly activates G(q) signaling pathways, but very little is known regarding the mechanism of signal transference ..
  17. Martinelli A, Knapp S, Anstee Q, Worku M, Tommasi A, Zucoloto S, et al. Effect of a thrombin receptor (protease-activated receptor 1, PAR-1) gene polymorphism in chronic hepatitis C liver fibrosis. J Gastroenterol Hepatol. 2008;23:1403-9 pubmed
    ..Analysis of IVS-14A/T showed no difference between genotypes. In conclusion, these findings suggest that PAR-1 receptor polymorphisms influence the progression of liver fibrosis. ..
  18. Wang W, Mize G, Zhang X, Takayama T. Kallikrein-related peptidase-4 initiates tumor-stroma interactions in prostate cancer through protease-activated receptor-1. Int J Cancer. 2010;126:599-610 pubmed publisher
  19. Arora P, Cuevas B, Russo A, Johnson G, Trejo J. Persistent transactivation of EGFR and ErbB2/HER2 by protease-activated receptor-1 promotes breast carcinoma cell invasion. Oncogene. 2008;27:4434-45 pubmed publisher
    ..Protease-activated receptor-1 (PAR1), a GPCR activated by extracellular proteases, is overexpressed in invasive breast cancer...
  20. Paing M, Temple B, Trejo J. A tyrosine-based sorting signal regulates intracellular trafficking of protease-activated receptor-1: multiple regulatory mechanisms for agonist-induced G protein-coupled receptor internalization. J Biol Chem. 2004;279:21938-47 pubmed
    Protease-activated receptor-1 (PAR1), a G protein-coupled receptor (GPCR) for thrombin, is irreversibly proteolytically activated, internalized, and then sorted to lysosomes and degraded...
  21. Tellez C, Davis D, Prieto V, Gershenwald J, Johnson M, McCarty M, et al. Quantitative analysis of melanocytic tissue array reveals inverse correlation between activator protein-2alpha and protease-activated receptor-1 expression during melanoma progression. J Invest Dermatol. 2007;127:387-93 pubmed
    ..These findings support our hypothesis that loss of AP-2 is a crucial event in the progression of human melanoma and contributes to the acquisition of the metastatic phenotype via upregulation of PAR-1. ..
  22. Zhang C, Srinivasan Y, Arlow D, Fung J, Palmer D, Zheng Y, et al. High-resolution crystal structure of human protease-activated receptor 1. Nature. 2012;492:387-92 pubmed publisher
    Protease-activated receptor 1 (PAR1) is the prototypical member of a family of G-protein-coupled receptors that mediate cellular responses to thrombin and related proteases...
  23. Riewald M, Petrovan R, Donner A, Mueller B, Ruf W. Activation of endothelial cell protease activated receptor 1 by the protein C pathway. Science. 2002;296:1880-2 pubmed
    ..PC (APC) was shown to use the endothelial cell PC receptor (EPCR) as a coreceptor for cleavage of protease activated receptor 1 (PAR1) on endothelial cells...
  24. Hein L, Ishii K, Coughlin S, Kobilka B. Intracellular targeting and trafficking of thrombin receptors. A novel mechanism for resensitization of a G protein-coupled receptor. J Biol Chem. 1994;269:27719-26 pubmed
    ..These observations reveal a novel trafficking mechanism for resensitizing the thrombin receptor as opposed to the internalization/recycling pathway of other G protein-coupled receptors. ..
  25. Leger A, Covic L, Kuliopulos A. Protease-activated receptors in cardiovascular diseases. Circulation. 2006;114:1070-7 pubmed
    ..The thrombin receptors PAR1 and PAR4 can be effectively targeted in animals in which acute or prolonged exposure to thrombin leads to ..
  26. Chin A, Lee W, Nusrat A, Vergnolle N, Parkos C. Neutrophil-mediated activation of epithelial protease-activated receptors-1 and -2 regulates barrier function and transepithelial migration. J Immunol. 2008;181:5702-10 pubmed
    ..These results suggest that protease-mediated epithelial PAR-1 and -2 activation, by migrating PMNs, induces signaling events that increase epithelial permeability thereby facilitates PMN transepithelial migration. ..
  27. Mathews I, Padmanabhan K, Ganesh V, Tulinsky A, Ishii M, Chen J, et al. Crystallographic structures of thrombin complexed with thrombin receptor peptides: existence of expected and novel binding modes. Biochemistry. 1994;33:3266-79 pubmed
    ..The physiological role for this unexpected intermolecular binding mode, if any, remains to be identified.(ABSTRACT TRUNCATED AT 400 WORDS) ..
  28. Russo A, Soh U, Paing M, Arora P, Trejo J. Caveolae are required for protease-selective signaling by protease-activated receptor-1. Proc Natl Acad Sci U S A. 2009;106:6393-7 pubmed publisher
    ..Thus, APC selective signaling and endothelial barrier protective effects are mediated through compartmentalization of PAR(1) in caveolae and a novel mechanism of PAR(1) signal regulation. ..
  29. Hernández N, Correa E, Avila E, Vela T, Pérez V. PAR1 is selectively over expressed in high grade breast cancer patients: a cohort study. J Transl Med. 2009;7:47 pubmed publisher
    The protease-activated receptor (PAR1) expression is correlated with the degree of invasiveness in cell lines. Nevertheless it has never been directed involved in breast cancer patients progression...
  30. Villares G, Dobroff A, Wang H, Zigler M, Melnikova V, Huang L, et al. Overexpression of protease-activated receptor-1 contributes to melanoma metastasis via regulation of connexin 43. Cancer Res. 2009;69:6730-7 pubmed publisher
    ..Indeed, Cx-43 expression was restored following PAR-1 rescue in PAR-1-silenced cells. Taken together, our data support the tumor promoting function of Cx-43 in melanoma. ..
  31. Bae J, Yang L, Manithody C, Rezaie A. The ligand occupancy of endothelial protein C receptor switches the protease-activated receptor 1-dependent signaling specificity of thrombin from a permeability-enhancing to a barrier-protective response in endothelial cells. Blood. 2007;110:3909-16 pubmed
    ..These results provide a new paradigm for understanding how PAR-1 and EPCR participate in protective signaling events in endothelial cells. ..
  32. Soto A, Trejo J. N-linked glycosylation of protease-activated receptor-1 second extracellular loop: a critical determinant for ligand-induced receptor activation and internalization. J Biol Chem. 2010;285:18781-93 pubmed publisher
    Protease-activated receptor-1 (PAR1) contains five N-linked glycosylation consensus sites as follows: three residing in the N terminus and two localized on the surface of the second extracellular loop (ECL2)...
  33. Villares G, Zigler M, Dobroff A, Wang H, Song R, Melnikova V, et al. Protease activated receptor-1 inhibits the Maspin tumor-suppressor gene to determine the melanoma metastatic phenotype. Proc Natl Acad Sci U S A. 2011;108:626-31 pubmed publisher
    ..Maspin promoter activity was significantly increased after PAR-1 silencing, suggesting that PAR1 negatively regulates Maspin at the transcriptional level...
  34. Massi D, Naldini A, Ardinghi C, Carraro F, Franchi A, Paglierani M, et al. Expression of protease-activated receptors 1 and 2 in melanocytic nevi and malignant melanoma. Hum Pathol. 2005;36:676-85 pubmed
    ..Conversely, the significance of PAR-2 up-regulation in both benign and malignant melanocytic lesions requires further research. ..
  35. Tellez C, McCarty M, Ruiz M, Bar Eli M. Loss of activator protein-2alpha results in overexpression of protease-activated receptor-1 and correlates with the malignant phenotype of human melanoma. J Biol Chem. 2003;278:46632-42 pubmed
    ..Taken together, our results provide strong evidence that loss of AP-2 correlates with overexpression of PAR-1, which in turn contributes to the acquisition of the malignant phenotype of human melanoma. ..
  36. Feistritzer C, Riewald M. Endothelial barrier protection by activated protein C through PAR1-dependent sphingosine 1-phosphate receptor-1 crossactivation. Blood. 2005;105:3178-84 pubmed
    ..Pro-inflammatory signaling by the blood coagulation protease thrombin through protease activated receptor-1 (PAR1) can disrupt endothelial barrier integrity, whereas the bioactive lipid sphingosine 1-phosphate (S1P) recently has ..
  37. Darmoul D, Gratio V, Devaud H, Peiretti F, Laburthe M. Activation of proteinase-activated receptor 1 promotes human colon cancer cell proliferation through epidermal growth factor receptor transactivation. Mol Cancer Res. 2004;2:514-22 pubmed
    ..growth factor for colon cancer cells through activation of the aberrantly expressed protease-activated receptor 1 (PAR1)...
  38. Chen B, Dores M, Grimsey N, Canto I, Barker B, Trejo J. Adaptor protein complex-2 (AP-2) and epsin-1 mediate protease-activated receptor-1 internalization via phosphorylation- and ubiquitination-dependent sorting signals. J Biol Chem. 2011;286:40760-70 pubmed publisher
    Signaling by protease-activated receptor-1 (PAR1), a G protein-coupled receptor (GPCR) for thrombin, is regulated by desensitization and internalization. PAR1 desensitization is mediated by ?-arrestins, like most classic GPCRs...
  39. Gigante B, Bellis A, Visconti R, Marino M, Morisco C, Trimarco V, et al. Retrospective analysis of coagulation factor II receptor (F2R) sequence variation and coronary heart disease in hypertensive patients. Arterioscler Thromb Vasc Biol. 2007;27:1213-9 pubmed
    ..05). F2R genetic variants may influence the natural history of CHD in patients at high risk of cardiovascular events. ..
  40. Salah Z, Maoz M, Pokroy E, Lotem M, Bar Shavit R, Uziely B. Protease-activated receptor-1 (hPar1), a survival factor eliciting tumor progression. Mol Cancer Res. 2007;5:229-40 pubmed
    Although ample evidence point to the central involvement of protease activated receptor-1 (PAR1) in tumor progression, little is known about the fate of the tumor when hPar1 is being silenced...
  41. Boire A, Covic L, Agarwal A, Jacques S, Sherifi S, Kuliopulos A. PAR1 is a matrix metalloprotease-1 receptor that promotes invasion and tumorigenesis of breast cancer cells. Cell. 2005;120:303-13 pubmed
    ..b>PAR1 is proposed to be involved in the invasive and metastatic processes of various cancers...
  42. Coughlin S, Vu T, Hung D, Wheaton V. Characterization of a functional thrombin receptor. Issues and opportunities. J Clin Invest. 1992;89:351-5 pubmed
  43. Ayoub M, Maurel D, Binet V, Fink M, Prezeau L, Ansanay H, et al. Real-time analysis of agonist-induced activation of protease-activated receptor 1/Galphai1 protein complex measured by bioluminescence resonance energy transfer in living cells. Mol Pharmacol. 2007;71:1329-40 pubmed
    ..Here, we used a BRET technique to monitor the coupling between the protease-activated receptor 1 (PAR1) and Galpha(i1) protein...
  44. Remillard C, Yuan J. PGE2 and PAR-1 in pulmonary fibrosis: a case of biting the hand that feeds you?. Am J Physiol Lung Cell Mol Physiol. 2005;288:L789-92 pubmed
  45. Nylander M, Osman A, Ramstrom S, Aklint E, Larsson A, Lindahl T. The role of thrombin receptors PAR1 and PAR4 for PAI-1 storage, synthesis and secretion by human platelets. Thromb Res. 2012;129:e51-8 pubmed publisher
    ..Human isolated platelets were incubated with thrombin (0.5 U/ml), PAR1-activating peptide (AP) (0.4-30 ?M) or PAR4-AP (1.5-300 ?M) for up to 24 hours...
  46. Auger J, Baptiste A, Benabbad I, Thierry G, Costa J, Amouyal M, et al. Genotype-Phenotype Relationship in Patients and Relatives with SHOX Region Anomalies in the French Population. Horm Res Paediatr. 2016;86:309-318 pubmed publisher
    ..7 (9.0; 15.9) years and mean height standard deviation score was -2.3 ± 1.1. A deletion of either SHOX or PAR1 or both was found in 74% of patients...
  47. Peng B, Zhu H, Klausen C, Ma L, Wang Y, Leung P. GnRH regulates trophoblast invasion via RUNX2-mediated MMP2/9 expression. Mol Hum Reprod. 2016;22:119-29 pubmed publisher
    ..Primary or immortalized (HTR-8/SVneo) EVT cells were treated alone or in combination with GnRH, GnRH antagonist Antide, MAPK kinase inhibitor ..
  48. García P, Ciavatta V, Fidler J, Woodbury A, Levy J, Tyor W. Concentration-Dependent Dual Role of Thrombin in Protection of Cultured Rat Cortical Neurons. Neurochem Res. 2015;40:2220-9 pubmed publisher
    ..Neurotoxic effects of thrombin do not involve activation of PAR receptors and thus separate pharmacologic manipulation of thrombin's receptor in the setting of direct thrombin inhibitors could be a potential neuroprotective strategy. ..
  49. Zhang S, Liu Y, WANG Z, Liu J, Gu Z, Xu Q, et al. PAR1‑mediated c‑Jun activation promotes heat stress‑induced early stage apoptosis of human umbilical vein endothelial cells. Mol Med Rep. 2017;15:2595-2603 pubmed publisher
    ..are involved in endothelial barrier function, are heat stressed, levels of protease‑activated receptor 1 (PAR1) are increased significantly...
  50. Liu J, Song G, Lin X, Pang X, Meng T. Upregulated unique long 16 binding protein 1 detected in preeclamptic placenta affects human extravillous trophoblast cell line (HTR-8/SVneo) invasion by modulating the function of uterine natural killer cells. Exp Ther Med. 2017;13:1447-1455 pubmed publisher
    ..The effects of ULBP1 on extravillous trophoblast cell line (HTR-8/SVneo) invasion mediated via uNK cells and the underlying mechanisms were investigated...
  51. Austin K, Nguyen N, Javid G, Covic L, Kuliopulos A. Noncanonical matrix metalloprotease-1-protease-activated receptor-1 signaling triggers vascular smooth muscle cell dedifferentiation and arterial stenosis. J Biol Chem. 2013;288:23105-15 pubmed publisher
    ..Protease-activated receptor-1 (PAR1) has been shown to play a role in vascular repair processes; however, little is known regarding its function or the ..
  52. Srinivasan S, Schiemer J, Zhang X, Chishti A, Le Breton G. Gα13 Switch Region 2 Binds to the Talin Head Domain and Activates αIIbβ3 Integrin in Human Platelets. J Biol Chem. 2015;290:25129-39 pubmed publisher
    ..Interestingly however, the dependence on Gα13SR1 signaling was limited to PAR1 receptors, and did not involve signaling through other important platelet GPCRs...
  53. Raque V, Carlos S, Eduardo R, Rafael B, Ángeles R, Adriana R, et al. Modification of immunological features in human platelets during sepsis. Immunol Invest. 2017;:1-16 pubmed publisher
    ..This research describes important features of platelets to help the understanding of the immunological role of these cells in sepsis...
  54. Chen D, Feng L, Hodges J, Lechuga T, Zhang H. Human trophoblast-derived hydrogen sulfide stimulates placental artery endothelial cell angiogenesis. Biol Reprod. 2017;97:478-489 pubmed publisher
    ..BeWo cells expressed both CBS and CTH proteins, while the first trimester villous trophoblast-originated HTR-8/SVneo cells expressed CTH protein only...
  55. van den Eshof B, Hoogendijk A, Simpson P, van Alphen F, Zanivan S, Mertens K, et al. Paradigm of Biased PAR1 (Protease-Activated Receptor-1) Activation and Inhibition in Endothelial Cells Dissected by Phosphoproteomics. Arterioscler Thromb Vasc Biol. 2017;37:1891-1902 pubmed publisher
    ..The predominant thrombin receptor is PAR1, and in endothelial cells (ECs), thrombin dynamically regulates a plethora of phosphorylation events...
  56. Hurley A, Smith M, Karpova T, Hasley R, Belkina N, Shaw S, et al. Enhanced effector function of CD8(+) T cells from healthy controls and HIV-infected patients occurs through thrombin activation of protease-activated receptor 1. J Infect Dis. 2013;207:638-50 pubmed publisher
    ..These findings suggest that thrombin mediates cross-talk between the coagulation system and the adaptive immune system at sites of vascular injury through increased T-cell motility and production of proinflammatory cytokines. ..
  57. Kay N, Bone N, Tschumper R, Howell K, Geyer S, Dewald G, et al. B-CLL cells are capable of synthesis and secretion of both pro- and anti-angiogenic molecules. Leukemia. 2002;16:911-9 pubmed
  58. Holinstat M, Voss B, Bilodeau M, McLaughlin J, Cleator J, Hamm H. PAR4, but not PAR1, signals human platelet aggregation via Ca2+ mobilization and synergistic P2Y12 receptor activation. J Biol Chem. 2006;281:26665-74 pubmed
    ..Thrombin is the most potent activator of platelets. Human platelets express two thrombin receptors, PAR1 and PAR4, both of which signal platelet activation...
  59. Ramstrom S, O Neill S, Dunne E, Kenny D. Annexin V binding to platelets is agonist, time and temperature dependent. Platelets. 2010;21:289-96 pubmed publisher
    ..The relative role of the thrombin protease-activated receptors (PARs), PAR1 and PAR4, together with different methods of platelet preparation on annexin V binding to platelets is unclear...
  60. Danahay H, Withey L, Poll C, van de Graaf S, Bridges R. Protease-activated receptor-2-mediated inhibition of ion transport in human bronchial epithelial cells. Am J Physiol Cell Physiol. 2001;280:C1455-64 pubmed
    ..By contrast, PAR2 activators added to the apical surface of the epithelia or PAR1 activators added to both the apical and basolateral surfaces were without effect...
  61. Bolton S, McNulty C, Thomas R, Hewitt C, Wardlaw A. Expression of and functional responses to protease-activated receptors on human eosinophils. J Leukoc Biol. 2003;74:60-8 pubmed
    ..To date, PAR1-4 have been identified, and there are several studies that have demonstrated the expression of PARs in airway ..
  62. Krenzer S, Peterziel H, Mauch C, Blaber S, Blaber M, Angel P, et al. Expression and function of the kallikrein-related peptidase 6 in the human melanoma microenvironment. J Invest Dermatol. 2011;131:2281-8 pubmed publisher
    ..intracellular Ca(2+) flux and tumor cell invasion critically depends on the protease-activated receptor 1 (PAR1)...
  63. Semeraro F, Ammollo C, Morrissey J, Dale G, Friese P, Esmon N, et al. Extracellular histones promote thrombin generation through platelet-dependent mechanisms: involvement of platelet TLR2 and TLR4. Blood. 2011;118:1952-61 pubmed publisher
    ..These data show that histone-activated platelets possess a procoagulant phenotype that drives plasma thrombin generation and suggest that TLR2 and TLR4 mediate the activation process. ..
  64. Schlagenhauf A, Haidl H, Pohl S, Weiss E, Leschnik B, Gallistl S, et al. Polyphosphate in Neonates: Less Shedding from Platelets and Divergent Prothrombotic Capacity Due to Lower TFPI Levels. Front Physiol. 2017;8:586 pubmed publisher
    ..A potential developmental mismatch should be considered when transfusing adult platelets into neonates...