SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on June 28, 2002; DOI 10.1182/blood-2002-02-0415. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-02-0415v1 100/13/4454    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 Wu, S.-Q. Articles by Aird, W. C. Search for Related Content PubMed PubMed Citation Articles by Wu, S.-Q. Articles by Aird, W. C. Related Collections Hemostasis, Thrombosis, and Vascular Biology Signal Transduction Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 December 2002, Vol. 100, No. 13, pp. 4454-4461 HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY The proximal serum response element in the Egr-1 promoter mediates response to thrombin in primary human endothelial cells Sheng-Qian Wu, Takashi Minami, Diana J. Donovan, and William C. Aird From the Department of Molecular Medicine, Beth Israel Deaconess Medical Center, Boston, MA. Thrombin signaling in endothelial cells provides an important link between coagulation and inflammation. We report here that thrombin induces endogenous Egr-1 mRNA and Egr-1 promoter activity in primary human endothelial cells by approximately 6-fold and 3-fold, respectively. In transient transfection assays, deletion of the 3' cluster of serum response elements (SREs), but not the 5' cluster of SREs, resulted in a loss of thrombin response. When coupled to a heterologous core promoter, a region spanning the 3' SRE cluster contained information for thrombin response, whereas a region spanning the 5' SRE cluster had no such effect. A point mutation of the most proximal SRE (SRE-1), but not of the proximal Ets motif or upstream SREs, abrogated the response to thrombin. In electrophoretic mobility shift assays, nuclear extracts from thrombin-treated cells displayed increased binding of total and phosphorylated serum response factor (SRF) to SRE-1. Thrombin-mediated induction of Egr-1 was blocked by inhibitors of MEK1/2, but not by inhibitors of protein kinase C, phosphatidylinositol 3-kinase, or p38 mitogen-activated protein kinase (MAPK). Taken together, these data suggest that thrombin induces Egr-1 expression in endothelial cells by a MAPK-dependent mechanism that involves an interaction between SRF and SRE-1. © 2002 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B.-S. Ding, N. Hong, M. Christofidou-Solomidou, C. Gottstein, S. M. Albelda, D. B. Cines, A. B. Fisher, and V. R. Muzykantov Anchoring Fusion Thrombomodulin to the Endothelial Lumen Protects against Injury-induced Lung Thrombosis and Inflammation Am. J. Respir. Crit. Care Med., August 1, 2009; 180(3): 247 - 256. [Abstract] [Full Text] [PDF] S. Flanagin, J. D. Nelson, D. G. Castner, O. Denisenko, and K. Bomsztyk Microplate-based chromatin immunoprecipitation method, Matrix ChIP: a platform to study signaling of complex genomic events Nucleic Acids Res., February 11, 2008; 36(3): e17 - e17. [Abstract] [Full Text] [PDF] C. M. Kinney, U. M. Chandrasekharan, L. Mavrakis, and P. E. DiCorleto VEGF and thrombin induce MKP-1 through distinct signaling pathways: role for MKP-1 in endothelial cell migration Am J Physiol Cell Physiol, January 1, 2008; 294(1): C241 - C250. [Abstract] [Full Text] [PDF] L. A. O'Brien, M. A. Richardson, S. F. Mehrbod, D. T. Berg, B. Gerlitz, A. Gupta, and B. W. Grinnell Activated Protein C Decreases Tumor Necrosis Factor Related Apoptosis-Inducing Ligand by an EPCR- Independent Mechanism Involving Egr-1/Erk-1/2 Activation Arterioscler Thromb Vasc Biol, December 1, 2007; 27(12): 2634 - 2641. [Abstract] [Full Text] [PDF] M. U. Latasa, D. Couton, C. Charvet, A. Lafanechere, J.-E. Guidotti, Z. Li, D. Tuil, D. Daegelen, C. Mitchell, and H. Gilgenkrantz Delayed liver regeneration in mice lacking liver serum response factor Am J Physiol Gastrointest Liver Physiol, April 1, 2007; 292(4): G996 - G1001. [Abstract] [Full Text] [PDF] L. M. Khachigian Early Growth Response-1 in Cardiovascular Pathobiology Circ. Res., February 3, 2006; 98(2): 186 - 191. [Abstract] [Full Text] [PDF] J. R.S. Day, K. M. Taylor, E. A. Lidington, J. C. Mason, D. O. Haskard, A. M. Randi, and R. C. Landis Aprotinin inhibits proinflammatory activation of endothelial cells by thrombin through the protease-activated receptor 1 J. Thorac. Cardiovasc. Surg., January 1, 2006; 131(1): 21 - 27. [Abstract] [Full Text] [PDF] M. Kamimura, C. Viedt, A. Dalpke, M. E. Rosenfeld, N. Mackman, D. M. Cohen, E. Blessing, M. Preusch, C. M. Weber, J. Kreuzer, et al. Interleukin-10 Suppresses Tissue Factor Expression in Lipopolysaccharide-Stimulated Macrophages via Inhibition of Egr-1 and a Serum Response Element/MEK-ERK1/2 Pathway Circ. Res., August 19, 2005; 97(4): 305 - 313. [Abstract] [Full Text] [PDF] S.-Q. Wu and W. C. Aird Thrombin, TNF-{alpha}, and LPS exert overlapping but nonidentical effects on gene expression in endothelial cells and vascular smooth muscle cells Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H873 - H885. [Abstract] [Full Text] [PDF] J. N. McLaughlin, M. R. Mazzoni, J. H. Cleator, L. Earls, A. L. Perdigoto, J. D. Brooks, J. A. S. Muldowney III, D. E. Vaughan, and H. E. Hamm Thrombin Modulates the Expression of a Set of Genes Including Thrombospondin-1 in Human Microvascular Endothelial Cells J. Biol. Chem., June 10, 2005; 280(23): 22172 - 22180. [Abstract] [Full Text] [PDF] Y. Liu, K. Pelekanakis, and M. J. Woolkalis Thrombin and Tumor Necrosis Factor {alpha} Synergistically Stimulate Tissue Factor Expression in Human Endothelial Cells: REGULATION THROUGH c-Fos AND c-Jun J. Biol. Chem., August 20, 2004; 279(34): 36142 - 36147. [Abstract] [Full Text] [PDF] J. W. Tullai, M. E. Schaffer, S. Mullenbrock, S. Kasif, and G. M. Cooper Identification of Transcription Factor Binding Sites Upstream of Human Genes Regulated by the Phosphatidylinositol 3-Kinase and MEK/ERK Signaling Pathways J. Biol. Chem., May 7, 2004; 279(19): 20167 - 20177. [Abstract] [Full Text] [PDF] T. Minami, A. Sugiyama, S.-Q. Wu, R. Abid, T. Kodama, and W. C. Aird Thrombin and Phenotypic Modulation of the Endothelium Arterioscler Thromb Vasc Biol, January 1, 2004; 24(1): 41 - 53. [Abstract] [Full Text] [PDF] A. B. Keeton, K. D. Bortoff, W. L. Bennett, J. L. Franklin, D. Y. Venable, and J. L. Messina Insulin-Regulated Expression of Egr-1 and Krox20: Dependence on ERK1/2 and Interaction with p38 and PI3-Kinase Pathways Endocrinology, December 1, 2003; 144(12): 5402 - 5410. [Abstract] [Full Text] [PDF]

	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020