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Blood, 1 November 2003, Vol. 102, No. 9, pp. 3224-3231. Prepublished online as a Blood First Edition Paper on July 17, 2003; DOI 10.1182/blood-2003-04-1130. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-04-1130v1 102/9/3224    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kataoka, H. Articles by Coughlin, S. R. Search for Related Content PubMed PubMed Citation Articles by Kataoka, H. Articles by Coughlin, S. R. Related Collections Signal Transduction Hemostasis, Thrombosis, and Vascular Biology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Protease-activated receptors 1 and 4 mediate thrombin signaling in endothelial cells Hiroshi Kataoka, Justin R. Hamilton, David D. McKemy, Eric Camerer, Yao-Wu Zheng, Abby Cheng, Courtney Griffin, and Shaun R. Coughlin From the Cardiovascular Research Institute and the Department of Medicine and Cellular and Molecular Pharmacology, University of California, San Francisco. Defining the relative importance of protease-activated receptors (PARs) for thrombin signaling in mouse endothelial cells is critical for a basic understanding of thrombin signaling in these cells and for the rational use of knockout mice to probe the roles of thrombin's actions on endothelial cells in vivo. We examined thrombin- and PAR agonist–induced increases in cytoplasmic calcium, phosphoinositide hydrolysis, extracellular signal-regulated kinase (ERK) phosphorylation, and gene expression in endothelial cells from wild-type and PAR-deficient mice. PAR1 and PAR4 agonists triggered responses in wild-type but not in Par1–/– and Par4–/– endothelial cells, respectively. Calcium imaging confirmed that a substantial fraction of individual endothelial cells responded to both agonists. Compared with wild-type cells, Par1–/– endothelial cells showed markedly decreased responses to low concentrations of thrombin, and cells that lacked both PAR1 and PAR4 showed no responses to even high concentrations of thrombin. Similar results were obtained when endothelial-dependent vasorelaxation of freshly isolated mouse aorta was used as an index of signaling in native endothelial cells. Thus PAR1 is the major thrombin receptor in mouse endothelial cells, but PAR4 also contributes. 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Chen, A. Carpenter, J. Abrahams, R. C. Chambers, R. I. Lechler, J. H. McVey, and A. Dorling Protease-activated receptor 1 activation is necessary for monocyte chemoattractant protein 1-dependent leukocyte recruitment in vivo J. Exp. Med., July 7, 2008; (2008) jem.20071427. [Abstract] [Full Text] [PDF] S. V. Pizzo Annexin 2/Factor Xa-Mediated Signal Transduction Circ. Res., February 29, 2008; 102(4): 389 - 391. [Full Text] [PDF] G. Bhattacharjee, J. Ahamed, R. Pawlinski, C. Liu, N. Mackman, W. Ruf, and T. S. Edgington Factor Xa Binding to Annexin 2 Mediates Signal Transduction via Protease-Activated Receptor 1 Circ. Res., February 29, 2008; 102(4): 457 - 464. [Abstract] [Full Text] [PDF] B. J. 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