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TNF‐alpha signaling collaborates with Src family kinases (SFK) to promote actin rearrangement and loss of barrier function in endothelial cells
Author(s) -
Adam Alejandro Pablo,
Vincent Peter,
Anthony Lowery
Publication year - 2011
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.25.1_supplement.1101.3
Subject(s) - proto oncogene tyrosine protein kinase src , microbiology and biotechnology , src family kinase , paxillin , actin , tumor necrosis factor alpha , chemistry , kinase , tyrosine protein kinase csk , focal adhesion , phosphorylation , biology , immunology , sh3 domain
TNF and SFKs have been implicated in the regulation of barrier function and tissue damage, including acute lung injury induced by LPS. We previously showed that activation of SFKs by overexpression of DN‐Csk did not increase by itself transendothelial cell electric resistance (TEER). We have not observed any activation of Src following the addition of TNF. Interestingly, we found that TNF synergizes with SFK to reduce TEER. A low dose of TNF (0.05 ng/ml) did not decrease TEER in control cells, but induced a strong decrease in cells expressing DN‐Csk. LacZ‐ and DN‐Csk‐expressing cells contain a cortical actin belt and very few stress fibers (SF). Low dose TNF produced thin SF but no loss in cortical actin present at the cell‐cell border. However, in cells expressing DN‐Csk, TNF induced short and very thick bundles of actin and promoted the shuttling of phosphorylated Src, paxillin, FAK, PYK2 and integrin beta3 to aggregates localized at the ends of the actin bundles in a configuration that resembled v‐Src‐overexpressing cells, suggesting and association between actin rearrangements and TEER. Blockade of these pathways may thus prove to be beneficial for the treatment of acute lung injury. Supported by grant RO1 HL77870