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Blood, 1 April 2004, Vol. 103, No. 7, pp. 2636-2644. Prepublished online as a Blood First Edition Paper on December 4, 2003; DOI 10.1182/blood-2003-05-1737. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-05-1737v1 103/7/2636    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 Chen, H.-C. Articles by Feener, E. P. Search for Related Content PubMed PubMed Citation Articles by Chen, H.-C. Articles by Feener, E. P. Related Collections Hemostasis, Thrombosis, and Vascular Biology Signal Transduction Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY MEK1,2 response element mediates angiotensin II—stimulated plasminogen activator inhibitor-1 promoter activation Hong-Chi Chen, and Edward P. Feener From the Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA. The MEK1,2 (MAPK/ERK kinase 1 and 2) pathway mediates the up-regulation of plasminogen activator inhibitor-1 (PAI-1) expression in vascular smooth muscle cells by a variety of hormones, including angiotensin II. Transfection of constitutively active MEKK-1, an upstream activator of the mitogen-activated protein (MAP) kinase pathways, was used to isolate an enhancer element located between -89 and -50 bp in PAI-1 promoter that was activated by MEKK-1 and selectively blocked by the MEK1,2 inhibitor PD98059. Mutational analysis revealed that the MEKK-1 response element (MRE) contained 2 cis-acting Sp1- and AP-1—like sequences, located between -75 to -70 and -63 to -52 bp, respectively. Overexpression of Sp1 enhanced MEKK-1—induced MRE promoter activity and a dominant-negative c-Fos blocked this Sp1 response. The combination of Sp1 and c-Jun or c-Fos was required to activate this MRE. Angiotensin II (Ang II) stimulation increased c-Fos, c-Jun, and Sp1 binding to the MRE by 100-, 4.9-, and 1.9-fold, respectively, and these responses were inhibited by PD98059 and AT1 receptor antagonist candesartan. Intravenous Ang II infusion in rats increased aortic c-Fos binding to the MRE. This MRE sequence mediated a 4-fold increase of MEK1,2-dependent PAI-1/luciferase mRNA expression by angiotensin II stimulation. This report identifies the MEK1,2 response element that mediates angiotensin II—stimulated PAI-1 promoter activation and shows that activation of this element requires Sp1 and AP-1 co-activation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. Rose, J. Bond, S. Tighe, M. J. Toth, T. L. Wellman, E. M. B. de Montiano, M. M. Lewinter, and K. M. Lounsbury Genes overexpressed in cerebral arteries following salt-induced hypertensive disease are regulated by angiotensin II, JunB, and CREB Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H1075 - H1085. [Abstract] [Full Text] [PDF] B. J. Xu, Y. Shyr, X. Liang, L.-j. Ma, E. M. Donnert, J. D. Roberts, X. Zhang, V. Kon, N. J. Brown, R. M. Caprioli, et al. Proteomic Patterns and Prediction of Glomerulosclerosis and Its Mechanisms J. Am. Soc. Nephrol., October 1, 2005; 16(10): 2967 - 2975. [Abstract] [Full Text] [PDF] Q. Liu, U. Moller, D. Flugel, and T. Kietzmann Induction of plasminogen activator inhibitor I gene expression by intracellular calcium via hypoxia-inducible factor-1 Blood, December 15, 2004; 104(13): 3993 - 4001. [Abstract] [Full Text] [PDF]

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