ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2014
Paxillin mediates stretch-induced Rho signaling and endothelial permeability via assembly of paxillin-p42/44MAPK-GEF-H1 complex.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Impact of physiological strain on lung epithelial cells by exposure to aerosolised quartz silica in a perfused bioreactor.Frontiers in bioengineering and biotechnology · 2026Article
- Alveolar epithelial paxillin in postnatal lung alveolar development.Biology open · 2025Article
- Cell-Material Interplay in Focal Adhesion Points.ACS applied materials & interfaces · 2024Article
- Paxillin knockout in mouse granulosa cells increases fecundity†.Biology of reproduction · 2023Article
- Hyperoxia but not high tidal volume contributes to ventilator-induced lung injury in healthy mice.BMC pulmonary medicine · 2023Article
- Direct active Fyn-paxillin interaction regulates vascular smooth muscle cell migration.Journal of smooth muscle research = Nihon Heikatsukin Gakkai kikanshi · 2023Review
- Role of Skin Stretch on Local Vascular Permeability in Murine and Cell Culture Models.Plastic and reconstructive surgery. Global open · 2022Article
- Secreted Extracellular Cyclophilin A Is a Novel Mediator of Ventilator-induced Lung Injury.American journal of respiratory and critical care medicine · 2021Article
- Cell Shape and Matrix Stiffness Impact Schwann Cell Plasticity via YAP/TAZ and Rho GTPases.International journal of molecular sciences · 2021Article
- Paxillin family of focal adhesion adaptor proteins and regulation of cancer cell invasion.International review of cell and molecular biology · 2020Article
- Biomechanical Forces and Oxidative Stress: Implications for Pulmonary Vascular Disease.Antioxidants & redox signaling · 2019Review
- Mechanosensitive Rap1 activation promotes barrier function of lung vascular endothelium under cyclic stretch.Molecular biology of the cell · 2019Article
- Mechanosensing and Mechanoregulation of Endothelial Cell Functions.Comprehensive Physiology · 2019Review
- Role of Cingulin in Agonist-induced Vascular Endothelial Permeability.The Journal of biological chemistry · 2016Article
- Selective Role of Vinculin in Contractile Mechanisms of Endothelial Permeability.American journal of respiratory cell and molecular biology · 2016Article
- Using cultured endothelial cells to study endothelial barrier dysfunction: Challenges and opportunities.American journal of physiology. Lung cellular and molecular physiology · 2016Review
- Chronic high-magnitude cyclic stretch stimulates EC inflammatory response via VEGF receptor 2-dependent mechanism.American journal of physiology. Lung cellular and molecular physiology · 2016Article
- Activation of Vascular Endothelial Growth Factor (VEGF) Receptor 2 Mediates Endothelial Permeability Caused by Cyclic Stretch.The Journal of biological chemistry · 2016Article
- Role of Krev Interaction Trapped-1 in Prostacyclin-Induced Protection against Lung Vascular Permeability Induced by Excessive Mechanical Forces and Thrombin Receptor Activating Peptide 6.American journal of respiratory cell and molecular biology · 2015Article
- Differential and opposing effects of imatinib on LPS- and ventilator-induced lung injury.American journal of physiology. Lung cellular and molecular physiology · 2015Article
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6 authors.
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Abstract
Suboptimal ventilator support or regional ventilation heterogeneity in inflamed lungs causes excessive tissue distension, which triggers stretch-induced pathological signaling and may lead to vascular leak and lung dysfunction. Focal adhesions (FAs) are cell-substrate adhesive complexes participating in cellular mechanotransduction and regulation of the Rho GTPase pathway. Stretch-induced Rho regulation remains poorly understood. We used human lung endothelial cells (ECs) exposed to pathological cyclic stretch (CS) at 18% distension to test the hypothesis that FA protein paxillin participates in CS-induced Rho activation by recruiting the Rho-specific guanine nucleotide exchange factor GEF-H1. CS induced phosphorylation of paxillin and activated p42/44-MAP kinase, Rho GTPase, and paxillin/GEF-H1/p42/44-MAPK association. CS caused nearly 2-fold increase in EC permeability, which was attenuated by paxillin knockdown. Expression of the paxillin-Y31/118F phosphorylation mutant decreased the CS-induced paxillin/GEF-H1 association (16.3 ± 4.1%), GEF-H1 activation (28.9 ± 9.2%), and EC permeability (28.7 ± 8.1%) but not CS-induced p42/44-MAPK activation. Inhibition of p42/44-MAPK suppressed CS-induced paxillin/GEF-H1 interactions (15.9 ± 7.9%), GEF-H1 activation (11.7 ± 4.3%), and disruption of EC monolayer. Expression of GEF-H1T678A lacking p42/44-MAPK phosphorylation site attenuated Rho activation (31.2±11.6%). We conclude that MAPK-dependent targeting of GEF-H1 to paxillin is involved in the regulation of CS-induced Rho signaling and EC permeability. This study proposes a novel concept of paxillin-GEF-H1-p42/44-MAPK module as a regulator of pathological mechanotransduction.-Gawlak, G., Tian, Y., O'Donnell, J. J., III, Tian, X., Birukova, A. A., Birukov, K. G. Paxillin mediates stretch-induced Rho signaling and endothelial permeability via assembly of paxillin-p42/44MAPK-GEF-H1 complex.
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