title: Enhanced interaction between focal adhesion and adherens junction proteins: involvement in sphingosine 1-phosphate-induced endothelial barrier enhancement.
abstract: Sphingosine 1-phosphate (S1P) is an important vascular barrier regulatory agonist which enhances the junctional integrity of human lung endothelial cell monolayers. We have now demonstrated that S1P induced cortical actin ring formation and redistribution of focal adhesion kinase (FAK) and paxillin to the cell periphery suggesting the critical role of cell-cell adhesion in endothelial barrier enhancement. Co-immunoprecipitation studies revealed increased association of VE-cadherin with FAK and paxillin in S1P-challenged human pulmonary artery endothelial cell (HPAEC) monolayers. Furthermore, S1P-induced enhancement of VE-cadherin interaction with alpha-catenin and beta-catenin was associated with the increased formation of FAK-beta-catenin protein complexes. Depletion of beta-catenin (siRNA) resulted in loss of S1P-mediated VE-cadherin association with FAK and paxillin rearrangement. Furthermore, transendothelial electrical resistance (an index of barrier function) demonstrated that beta-catenin siRNA significantly attenuated S1P-induced barrier enhancement. These results demonstrate a mechanism of S1P-induced endothelial barrier enhancement via beta-catenin-linked adherens junction and focal adhesion interaction.
authors.affiliation: Department of Medicine, Division of Biological Sciences, The University of Chicago, 5841 Maryland Ave., Chicago, IL 60637-1470, USA.
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Sun
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Shikata
authors.forename: Lichun
authors.initials: L
authors.lastname: Wang
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Ohmori
authors.forename: Naoko
authors.initials: N
authors.lastname: Watanabe
authors.forename: Jun
authors.initials: J
authors.lastname: Wada
authors.forename: Kenichi
authors.initials: K
authors.lastname: Shikata
authors.forename: Konstantin G
authors.initials: KG
authors.lastname: Birukov
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Makino
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Jacobson
authors.forename: Steven M
authors.initials: SM
authors.lastname: Dudek
authors.forename: Joe G N
authors.initials: JG
authors.lastname: Garcia