SEARCH:   Advanced

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 (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 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 Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 26, 2004 Accepted September 6, 2004 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* Center for Excellence in Vascular Biology, Dept. of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA * Corresponding author; email: tmayadas{at}rics.bwh.harvard.edu. 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 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 downregulation of Rho GTPase activation suggesting cross-talk between Rap and Rho GTPases. 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: G. Borland, R. J. Bird, T. M. Palmer, and S. J. Yarwood Activation of Protein Kinase C{alpha} by EPAC1 Is Required for the ERK- and CCAAT/Enhancer-binding Protein {beta}-dependent Induction of the SOCS-3 Gene by Cyclic AMP in COS1 Cells J. Biol. Chem., June 26, 2009; 284(26): 17391 - 17403. [Abstract] [Full Text] [PDF] B. Ponsioen, M. Gloerich, L. Ritsma, H. Rehmann, J. L. Bos, and K. Jalink Direct Spatial Control of Epac1 by Cyclic AMP Mol. Cell. Biol., May 15, 2009; 29(10): 2521 - 2531. [Abstract] [Full Text] [PDF] G. Carmona, S. Gottig, A. Orlandi, J. Scheele, T. Bauerle, M. Jugold, F. Kiessling, R. Henschler, A. M. Zeiher, S. Dimmeler, et al. Role of the small GTPase Rap1 for integrin activity regulation in endothelial cells and angiogenesis Blood, January 8, 2009; 113(2): 488 - 497. [Abstract] [Full Text] [PDF] A. V. Gore, M. G. Lampugnani, L. Dye, E. Dejana, and B. M. Weinstein Combinatorial interaction between CCM pathway genes precipitates hemorrhagic stroke Dis. Model. Mech., November 1, 2008; 1(4-5): 275 - 281. [Abstract] [Full Text] [PDF] J. Qiao, O. Holian, B.-S. Lee, F. Huang, J. Zhang, and H. Lum Phosphorylation of GTP dissociation inhibitor by PKA negatively regulates RhoA Am J Physiol Cell Physiol, November 1, 2008; 295(5): C1161 - C1168. [Abstract] [Full Text] [PDF] S. K. Huang, S. H. Wettlaufer, J. Chung, and M. Peters-Golden Prostaglandin E2 Inhibits Specific Lung Fibroblast Functions via Selective Actions of PKA and Epac-1 Am. J. Respir. Cell Mol. Biol., October 1, 2008; 39(4): 482 - 489. [Abstract] [Full Text] [PDF] F. A. Sanchez, D. D. Kim, R. G. Duran, C. J. Meininger, and W. N. Duran Internalization of eNOS via caveolae regulates PAF-induced inflammatory hyperpermeability to macromolecules Am J Physiol Heart Circ Physiol, October 1, 2008; 295(4): H1642 - H1648. [Abstract] [Full Text] [PDF] J. Yan, F. Li, D. A. Ingram, and L. A. Quilliam Rap1a Is a Key Regulator of Fibroblast Growth Factor 2-Induced Angiogenesis and Together with Rap1b Controls Human Endothelial Cell Functions Mol. Cell. Biol., September 15, 2008; 28(18): 5803 - 5810. [Abstract] [Full Text] [PDF] 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. Yuan VE-cadherin and {beta}-catenin binding dynamics during histamine-induced endothelial hyperpermeability Am J Physiol Cell Physiol, April 1, 2008; 294(4): C977 - C984. [Abstract] [Full Text] [PDF] R. H. Adamson, J. C. Ly, R. K. Sarai, J. F. Lenz, A. Altangerel, D. Drenckhahn, and F. E. Curry Epac/Rap1 pathway regulates microvascular hyperpermeability induced by PAF in rat mesentery Am J Physiol Heart Circ Physiol, March 1, 2008; 294(3): H1188 - H1196. [Abstract] [Full Text] [PDF] S. Sehrawat, X. Cullere, S. Patel, J. Italiano Jr., and T. N. Mayadas Role of Epac1, an Exchange Factor for Rap GTPases, in Endothelial Microtubule Dynamics and Barrier Function Mol. Biol. Cell, March 1, 2008; 19(3): 1261 - 1270. [Abstract] [Full Text] [PDF] M. Chrzanowska-Wodnicka, A. E. Kraus, D. Gale, G. C. White II, and J. VanSluys Defective angiogenesis, endothelial migration, proliferation, and MAPK signaling in Rap1b-deficient mice Blood, March 1, 2008; 111(5): 2647 - 2656. [Abstract] [Full Text] [PDF] H. Ghandour, X. Cullere, A. Alvarez, F. W. Luscinskas, and T. N. Mayadas Essential role for Rap1 GTPase and its guanine exchange factor CalDAG-GEFI in LFA-1 but not VLA-4 integrin mediated human T-cell adhesion Blood, November 15, 2007; 110(10): 3682 - 3690. [Abstract] [Full Text] [PDF] M. Brock, F. Fan, F. C. Mei, S. Li, C. Gessner, V. L. Woods Jr., and X. Cheng Conformational Analysis of Epac Activation Using Amide Hydrogen/Deuterium Exchange Mass Spectrometry J. Biol. Chem., November 2, 2007; 282(44): 32256 - 32263. [Abstract] [Full Text] [PDF] G.P. van Nieuw Amerongen, C.M.L. Beckers, I.D. Achekar, S. Zeeman, R.J.P. Musters, and V.W.M. van Hinsbergh Involvement of Rho Kinase in Endothelial Barrier Maintenance Arterioscler Thromb Vasc Biol, November 1, 2007; 27(11): 2332 - 2339. [Abstract] [Full Text] [PDF] A. Glading, J. Han, R. A. Stockton, and M. H. Ginsberg KRIT-1/CCM1 is a Rap1 effector that regulates endothelial cell cell junctions J. Cell Biol., October 22, 2007; 179(2): 247 - 254. [Abstract] [Full Text] [PDF] Y. Fang and M. E. Olah Cyclic AMP-Dependent, Protein Kinase A-Independent Activation of Extracellular Signal-Regulated Kinase 1/2 Following Adenosine Receptor Stimulation in Human Umbilical Vein Endothelial Cells: Role of Exchange Protein Activated by cAMP 1 (Epac1) J. Pharmacol. Exp. Ther., September 1, 2007; 322(3): 1189 - 1200. [Abstract] [Full Text] [PDF] R. Pasvolsky, S. W. Feigelson, S. S. Kilic, A. J. Simon, G. Tal-Lapidot, V. Grabovsky, J. R. Crittenden, N. Amariglio, M. Safran, A. M. Graybiel, et al. A LAD-III syndrome is associated with defective expression of the Rap-1 activator CalDAG-GEFI in lymphocytes, neutrophils, and platelets J. Exp. Med., July 9, 2007; 204(7): 1571 - 1582. [Abstract] [Full Text] [PDF] G. P. van Nieuw Amerongen and V. W.M. van Hinsbergh Endogenous RhoA Inhibitor Protects Endothelial Barrier Circ. Res., July 6, 2007; 101(1): 7 - 9. [Full Text] [PDF] J. Hong, R. C. Doebele, M. W. Lingen, L. A. Quilliam, W.-J. Tang, and M. R. Rosner Anthrax Edema Toxin Inhibits Endothelial Cell Chemotaxis via Epac and Rap1 J. Biol. Chem., July 6, 2007; 282(27): 19781 - 19787. [Abstract] [Full Text] [PDF] A. A. Birukova, I. Malyukova, V. Poroyko, and K. G. Birukov Paxillin-beta-catenin interactions are involved in Rac/Cdc42-mediated endothelial barrier-protective response to oxidized phospholipids Am J Physiol Lung Cell Mol Physiol, July 1, 2007; 293(1): L199 - L211. [Abstract] [Full Text] [PDF] M. Sircar, P. F. Bradfield, M. Aurrand-Lions, R. J. Fish, P. Alcaide, L. Yang, G. Newton, D. Lamont, S. Sehrawat, T. Mayadas, et al. Neutrophil Transmigration under Shear Flow Conditions In Vitro Is Junctional Adhesion Molecule-C Independent J. Immunol., May 1, 2007; 178(9): 5879 - 5887. [Abstract] [Full Text] [PDF] M. J. Lorenowicz, M. Fernandez-Borja, and P. L. Hordijk cAMP Signaling in Leukocyte Transendothelial Migration Arterioscler Thromb Vasc Biol, May 1, 2007; 27(5): 1014 - 1022. [Abstract] [Full Text] [PDF] M. R. H. Kooistra, N. Dube, and J. L. Bos Rap1: a key regulator in cell-cell junction formation J. Cell Sci., January 1, 2007; 120(1): 17 - 22. [Abstract] [Full Text] [PDF] S. K. Quadri and J. Bhattacharya Resealing of endothelial junctions by focal adhesion kinase Am J Physiol Lung Cell Mol Physiol, January 1, 2007; 292(1): L334 - L342. [Abstract] [Full Text] [PDF] M. J. Lorenowicz, J. van Gils, M. de Boer, P. L. Hordijk, and M. Fernandez-Borja Epac1-Rap1 signaling regulates monocyte adhesion and chemotaxis J. Leukoc. Biol., December 1, 2006; 80(6): 1542 - 1552. [Abstract] [Full Text] [PDF] V. V. Orlova, M. Economopoulou, F. Lupu, S. Santoso, and T. Chavakis Junctional adhesion molecule-C regulates vascular endothelial permeability by modulating VE-cadherin-mediated cell-cell contacts J. Exp. Med., November 27, 2006; 203(12): 2703 - 2714. [Abstract] [Full Text] [PDF] R. A. Bundey and P. A. Insel Adenylyl Cyclase 6 Overexpression Decreases the Permeability of Endothelial Monolayers via Preferential Enhancement of Prostacyclin Receptor Function Mol. Pharmacol., November 1, 2006; 70(5): 1700 - 1707. [Abstract] [Full Text] [PDF] W. A. Sands, H. D. Woolson, G. R. Milne, C. Rutherford, and T. M. Palmer Exchange Protein Activated by Cyclic AMP (Epac)-Mediated Induction of Suppressor of Cytokine Signaling 3 (SOCS-3) in Vascular Endothelial Cells. Mol. Cell. Biol., September 1, 2006; 26(17): 6333 - 6346. [Abstract] [Full Text] [PDF] M. G. Rondaij, R. Bierings, A. Kragt, J. A. van Mourik, and J. Voorberg Dynamics and Plasticity of Weibel-Palade Bodies in Endothelial Cells Arterioscler Thromb Vasc Biol, May 1, 2006; 26(5): 1002 - 1007. [Abstract] [Full Text] [PDF] R. Fischmeister Is cAMP Good or Bad?: Depends on Where It's Made Circ. Res., March 17, 2006; 98(5): 582 - 584. [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. Mochizuki Enhanced Functional Gap Junction Neoformation by Protein Kinase A-Dependent and Epac-Dependent Signals Downstream of cAMP in Cardiac Myocytes Circ. Res., September 30, 2005; 97(7): 655 - 662. [Abstract] [Full Text] [PDF] T. Yamada, T. Sakisaka, S. Hisata, T. Baba, and Y. Takai RA-RhoGAP, Rap-activated Rho GTPase-activating Protein Implicated in Neurite Outgrowth through Rho J. Biol. Chem., September 23, 2005; 280(38): 33026 - 33034. [Abstract] [Full Text] [PDF] E. S. Wittchen, R. A. Worthylake, P. Kelly, P. J. Casey, L. A. Quilliam, and K. Burridge Rap1 GTPase Inhibits Leukocyte Transmigration by Promoting Endothelial Barrier Function J. Biol. Chem., March 25, 2005; 280(12): 11675 - 11682. [Abstract] [Full Text] [PDF]

	Copyright © 2004 by American Society of Hematology         Online ISSN: 1528-0020