Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. STKE, 13 November 2007
Vol. 2007, Issue 412, p. re8
[DOI: 10.1126/stke.4122007re8]


Dual Regulation of Endothelial Junctional Permeability

Yulia A. Komarova{dagger}, Dolly Mehta{dagger}, and Asrar B. Malik*

Department of Pharmacology and Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, IL 60612, USA.
{dagger}These authors contributed equally to this work.

Abstract: G protein–coupled receptors (GPCRs) of endothelial cells transmit diverse intracellular signals that regulate adherens junction (AJ) permeability. Increased endothelial permeability contributes to pathological processes such as inflammation, atherogenesis, and acute lung injury. Thrombin, a serine protease, and sphingosine-1-phosphate (S1P), a bioactive lipid, regulate endothelial barrier function by activating their respective GPCRs—the protease-activated receptor PAR1 and the S1P receptor S1P1—which initiate intracellular signals that regulate AJ integrity and cytoskeleton organization. The distinct patterns of PAR1 and S1P1 signal transduction underlie the functional antagonism between thrombin and S1P. Evidence points to a role for activation of the S1P1 receptor that is induced by PAR1-mediated signaling in the mechanism of AJ reannealing and endothelial barrier repair. Understanding the molecular basis of AJ integrity in the context of inflammation is important in developing novel anti-inflammatory therapeutics. This Review provides a working model for molecular mechanisms for the dual regulation of endothelial barrier function.

*Corresponding author. E-mail, abmalik{at}

Citation: Y. A. Komarova, D. Mehta, A. B. Malik, Dual Regulation of Endothelial Junctional Permeability. Sci. STKE 2007, re8 (2007).

Read the Full Text

Evidence of a common mechanism of disassembly of adherens junctions through G{alpha}13 targeting of VE-cadherin.
H. Gong, X. Gao, S. Feng, M. R. Siddiqui, A. Garcia, M. G. Bonini, Y. Komarova, S. M. Vogel, D. Mehta, and A. B. Malik (2014)
J. Exp. Med. 211, 579-591
   Abstract »    Full Text »    PDF »
Cofactoring and Dimerization of Proteinase-Activated Receptors.
H. Lin, A. P. Liu, T. H. Smith, and J. Trejo (2013)
Pharmacol. Rev. 65, 1198-1213
   Abstract »    Full Text »    PDF »
Foxc1 is required by pericytes during fetal brain angiogenesis.
J. A. Siegenthaler, Y. Choe, K. P. Patterson, I. Hsieh, D. Li, S.-C. Jaminet, R. Daneman, T. Kume, E. J. Huang, and S. J. Pleasure (2013)
Biology Open 2, 647-659
   Abstract »    Full Text »    PDF »
Biased agonism of protease-activated receptor 1 by activated protein C caused by noncanonical cleavage at Arg46.
L. O. Mosnier, R. K. Sinha, L. Burnier, E. A. Bouwens, and J. H. Griffin (2012)
Blood 120, 5237-5246
   Abstract »    Full Text »    PDF »
Sphingosine-1-Phosphate Receptor-1 Controls Venous Endothelial Barrier Integrity in Zebrafish.
C. Tobia, P. Chiodelli, S. Nicoli, P. Dell'Era, S. Buraschi, S. Mitola, E. Foglia, P. B. van Loenen, A. E. Alewijnse, and M. Presta (2012)
Arterioscler Thromb Vasc Biol 32, e104-e116
   Abstract »    Full Text »    PDF »
Crosstalk Between Reticular Adherens Junctions and Platelet Endothelial Cell Adhesion Molecule-1 Regulates Endothelial Barrier Function.
L. Fernandez-Martin, B. Marcos-Ramiro, C. L. Bigarella, M. Graupera, R. J. Cain, N. Reglero-Real, A. Jimenez, E. Cernuda-Morollon, I. Correas, S. Cox, et al. (2012)
Arterioscler Thromb Vasc Biol 32, e90-e102
   Abstract »    Full Text »    PDF »
Activated protein C promotes protease-activated receptor-1 cytoprotective signaling through {beta}-arrestin and dishevelled-2 scaffolds.
U. J. K. Soh and J. Trejo (2011)
PNAS 108, E1372-E1380
   Abstract »    Full Text »    PDF »
Mechanisms of lung endothelial barrier disruption induced by cigarette smoke: role of oxidative stress and ceramides.
K. S. Schweitzer, H. Hatoum, M. B. Brown, M. Gupta, M. J. Justice, B. Beteck, M. Van Demark, Y. Gu, R. G. Presson Jr., W. C. Hubbard, et al. (2011)
Am J Physiol Lung Cell Mol Physiol 301, L836-L846
   Abstract »    Full Text »    PDF »
Leukocyte rolling and adhesion via ICAM-1 signals to endothelial permeability. Focus on "Leukocyte rolling and adhesion both contribute to regulation of microvascular permeability to albumin via ligation of ICAM-1".
M. R. Williams and F. W. Luscinskas (2011)
Am J Physiol Cell Physiol 301, C777-C779
   Full Text »    PDF »
Insulin regulates its own delivery to skeletal muscle by feed-forward actions on the vasculature.
E. J. Barrett, H. Wang, C. T. Upchurch, and Z. Liu (2011)
Am J Physiol Endocrinol Metab 301, E252-E263
   Abstract »    Full Text »    PDF »
Relative contribution of PECAM-1 adhesion and signaling to the maintenance of vascular integrity.
J. R. Privratsky, C. M. Paddock, O. Florey, D. K. Newman, W. A. Muller, and P. J. Newman (2011)
J. Cell Sci. 124, 1477-1485
   Abstract »    Full Text »    PDF »
Factor VIIa bound to endothelial cell protein C receptor activates protease activated receptor-1 and mediates cell signaling and barrier protection.
P. Sen, R. Gopalakrishnan, H. Kothari, S. Keshava, C. A. Clark, C. T. Esmon, U. R. Pendurthi, and L. V. M. Rao (2011)
Blood 117, 3199-3208
   Abstract »    Full Text »    PDF »
G Protein {beta}{gamma} Subunits Regulate Cell Adhesion through Rap1a and Its Effector Radil.
S. M. Ahmed, A. M. Daulat, A. Meunier, and S. Angers (2010)
J. Biol. Chem. 285, 6538-6551
   Abstract »    Full Text »    PDF »
Plugging Vascular Leak by Sphingosine Kinase From Bone Marrow Progenitor Cells.
T. Hla (2009)
Circ. Res. 105, 614-616
   Full Text »    PDF »
High-Density Lipoprotein Transport Through Aortic Endothelial Cells Involves Scavenger Receptor BI and ATP-Binding Cassette Transporter G1.
L. Rohrer, P. M. Ohnsorg, M. Lehner, F. Landolt, F. Rinninger, and A. von Eckardstein (2009)
Circ. Res. 104, 1142-1150
   Abstract »    Full Text »    PDF »
Caveolae are required for protease-selective signaling by protease-activated receptor-1.
A. Russo, U. J. K. Soh, M. M. Paing, P. Arora, and J. Trejo (2009)
PNAS 106, 6393-6397
   Abstract »    Full Text »    PDF »
Kaposi's Sarcoma-Associated Herpesvirus Disrupts Adherens Junctions and Increases Endothelial Permeability by Inducing Degradation of VE-Cadherin.
L.-W. Qian, W. Greene, F. Ye, and S.-J. Gao (2008)
J. Virol. 82, 11902-11912
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882