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Blood, 1 March 2005, Vol. 105, No. 5, pp. 1950-1955. Prepublished online as a Blood First Edition Paper on September 16, 2004; DOI 10.1182/blood-2004-05-1987. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-05-1987v1 105/5/1950    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 Cullere, X. Articles by Mayadas, T. N. Search for Related Content PubMed PubMed Citation Articles by Cullere, X. Articles by Mayadas, T. N. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Cytoskeleton Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Regulation of vascular endothelial barrier function by Epac, a cAMP-activated exchange factor for Rap GTPase Xavier Cullere, Sunil K. Shaw, Lorna Andersson, Junichi Hirahashi, Francis W. Luscinskas, and Tanya N. Mayadas From the Center for Excellence in Vascular Biology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA. Endothelial cell-cell junctional proteins and cortical actin are of central importance for regulating vascular permeability. Rap1, a member of the Ras family of GTPases, is enriched at endothelial cell-cell contacts and activated by cyclic AMP (cAMP) through a PKA-independent pathway. Activation of a cAMP-inducible guanine-exchange factor for Rap, Epac, results in markedly enhanced basal endothelial barrier function by increasing cortical actin and subsequent redistribution of adherens and tight junctional molecules to cell-cell contacts. Activation of Epac also counteracts thrombin-induced hyperpermeability through down-regulation of Rho GTPase activation, suggesting cross-talk between Rap and Rho GT-Pases. Thus, Epac/Rap activation represents a new pathway for regulating endothelial cell barrier function. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. Dejana, F. Orsenigo, and M. G. Lampugnani The role of adherens junctions and VE-cadherin in the control of vascular permeability J. Cell Sci., July 1, 2008; 121(13): 2115 - 2122. [Abstract] [Full Text] [PDF] M. Guo, J. W. Breslin, M. H. Wu, C. J. Gottardi, and S. Y. 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[Full Text] [PDF] R H Adamson, J C Ly, D Drenckhahn, and F E Curry Activation of Epac/Rap1 attenuates venular permeability response to platelet activating factor (PAF) in vivo FASEB J, March 1, 2006; 20(4): A706 - A706. [Abstract] [Full Text] M. Duchniewicz, T. Zemojtel, M. Kolanczyk, S. Grossmann, J. S. Scheele, and F. J. T. Zwartkruis Rap1A-Deficient T and B Cells Show Impaired Integrin-Mediated Cell Adhesion Mol. Cell. Biol., January 15, 2006; 26(2): 643 - 653. [Abstract] [Full Text] [PDF] D. Mehta and A. B. Malik Signaling Mechanisms Regulating Endothelial Permeability Physiol Rev, January 1, 2006; 86(1): 279 - 367. [Abstract] [Full Text] [PDF] R. H. Adamson and F. E. Curry Ang-1: Tie-ing up endothelial adhesion? Am J Physiol Heart Circ Physiol, January 1, 2006; 290(1): H74 - H76. [Full Text] [PDF] S. Somekawa, S. Fukuhara, Y. Nakaoka, H. Fujita, Y. Saito, and N. 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