A critical role for phosphatidylinositol (3,4,5)-trisphosphate-dependent Rac exchanger 1 in endothelial junction disruption and vascular hyperpermeability.
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...lymerization of branched actin networks within lamellipodia protrusions,(187,189,270,294) Cdc42 facilitates polymerization of linear F-actin filaments into filopodia.(295,296) On activation,...
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...through phosphatidylinositol (3,4,5)-trisphosphate–dependent Rac exchanger 1 (P-Rex1).(296) In this case, Rac1 signals through...
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157 citations
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...Rac1 can either positively or negatively regulate barrier function in a stimulus dependent manner [48-50] whilst Rap1, enhances barrier function via inhibition of Rho and activation of Cdc42 [51 52] as well as a co-...
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...In human endothelial cells, P-Rex knockdown, expression of dominant-negative Rac and specific Rac inhibitors abrogate ROS production in response to TNF (37)....
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...Rac-induced ROS regulate endothelial permeability by elevating the tyrosine phosphorylation of VE-cadherin (68), which prevents the binding of β-catenin and p120-catenin and results in inhibition of endothelial barrier function (37, 69, 70)....
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...Upstream of Rac, the Rac GEFs Vav, Tiam-1, Trio and P-Rex, are activated in response to TNF (37, 39, 40)....
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...Rac activity increases during the first minutes of TNF activation (21, 37) but decreases during longterm stimulation (32, 38)....
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...However, to date, there has been no comparative study of the relative contribution of each of these GEFs to TNF-induced endothelial barrier disturbance (37, 40)....
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References
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"A critical role for phosphatidylino..." refers background or methods in this paper
...Phosphatidylinositol (3,4,5)-trisphosphate–dependent Rac exchanger 1 (P-Rex1) regulates tumor necrosis factor (TNF)-α–induced reactive oxygen species (ROS) production....
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...Role for phosphatidylinositol (3,4,5)-trisphosphate– dependent Rac exchanger 1 (P-Rex1) in tumor necrosis factor (TNF)-α–induced Rac activation....
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...Objective: By investigating phosphatidylinositol (3,4,5)-trisphosphate–dependent Rac exchanger 1 (P-Rex1), one of the Rac-specific guanine nucleotide exchange factors previously known for G protein–coupled receptor signaling, we sought to determine whether Rac-guanine nucleotide exchange factor is nodal for signal integration and potential target for drug intervention....
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...Key Words: acute lung injury ◼ endothelial dysfunction ◼ guanine nucleotide exchange factors ◼ pulmonary edema ◼ reactive oxygen species ◼ small GTPases ◼ vascular permeability A Critical Role for Phosphatidylinositol (3,4,5)-Trisphosphate–Dependent Rac Exchanger 1 in Endothelial Junction Disruption and Vascular Hyperpermeability...
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...Tumor necrosis factor (TNF)-α induces phosphoinositide 3-kinase–dependent membrane translocation of phosphatidylinositol (3,4,5)-trisphosphate–dependent Rac exchanger 1 (P-Rex1)....
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663 citations