Premium
Lung endothelial barrier restoration by interactions of β‐catenin and focal adhesion kinase
Author(s) -
Quadri Sadiqa K,
Bhattacharya Jahar
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a752
Subject(s) - paxillin , focal adhesion , catenin , ptk2 , chemistry , microbiology and biotechnology , monolayer , immunoprecipitation , biophysics , kinase , biology , biochemistry , signal transduction , protein kinase a , wnt signaling pathway , mitogen activated protein kinase kinase , gene
Mechanisms that restore lung endothelial (EC) barrier properties are poorly understood. To determine the role of β‐catenin in barrier restoration, we grew monolayers of rat lung microvascular EC (RLMEC) in inserts and we quantified barrier responses to continuous H 2 O 2 (100 μM) exposure in terms of the trans‐monolayer electrical resistance (TER ohms.cm 2 ). In wild type monolayers (mean±S.E.; n=4), H 2 O 2 decreased TER from a baseline of 32±3, by 5±2 in 10 min, following by return to baseline in 30 min (P<0.5). Immunoprecipitation experiments indicated that the baseline co‐association of β‐catenin with the focal adhesion protein, paxillin was lost after 5 min of H 2 O 2 exposure, but re‐established after 20 min (P<.05). However, in RLMEC monolayers expressing a mutant form of the focal adhesion kinase (FAK del ) that inhibits FAK activity (n=4), H 2 O 2 induced progressive TER decreases that failed to recover to baseline (P<0.05). Moreover, in FAK del cells β‐catenin did not associate with paxillin (P<0.05). We conclude that the H 2 O 2 ‐induced biphasic TER response resulted from the phasic dissociation and association of β‐catenin with paxillin. We speculate, dissociation of β‐catenin from focal adhesion proteins opens the EC barrier. FAK activation re‐establishes β‐catenin’s interaction with focal adhesion proteins, thereby restoring the barrier (HL36024, HL57556).