ArticleMolecular and cellular biology2007
GDI-1 phosphorylation switch at serine 96 induces RhoA activation and increased endothelial permeability.
Article in Molecular and cellular biology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 66 citations in OpenAlex.
- Phosphorylation induces altered protonation states and allosterically regulates Rac1-RhoGDI complex.Protein science : a publication of the Protein Society · 2026Article
- Endothelial Stiffening Induced by CD36-Mediated Lipid Uptake Leads to Endothelial Barrier Disruption and Contributes to Atherosclerotic Lesions.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
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- Molecular mechanism of regulation of RhoA GTPase by phosphorylation of RhoGDI.Biophysical journal · 2024Article
- DOCK4 Regulation of Rho GTPases Mediates Pulmonary Vascular Barrier Function.Arteriosclerosis, thrombosis, and vascular biology · 2022Article
- Rac-maninoff and Rho-vel: The symphony of Rho-GTPase signaling at excitatory synapses.Small GTPases · 2022Article
- Binding of the Andes Virus Nucleocapsid Protein to RhoGDI Induces the Release and Activation of the Permeability Factor RhoA.Journal of virology · 2021Article
- The complexities of PKCα signaling in cancer.Advances in biological regulation · 2021Review
- RHOA in Gastric Cancer: Functional Roles and Therapeutic Potential.Frontiers in genetics · 2019Review
- Proatherogenic Flow Increases Endothelial Stiffness via Enhanced CD36-Mediated Uptake of Oxidized Low-Density Lipoproteins.Arteriosclerosis, thrombosis, and vascular biology · 2018Article
- A functional siRNA screen identifies RhoGTPase-associated genes involved in thrombin-induced endothelial permeability.PloS one · 2018Article
- IPCellular and molecular life sciences : CMLS · 2017Review
- oxLDL induces endothelial cell proliferation via Rho/ROCK/Akt/p27American journal of physiology. Cell physiology · 2017Article
- The protective role of MLCP-mediated ERM dephosphorylation in endotoxin-induced lung injury in vitro and in vivo.Scientific reports · 2016Article
- The Andes Virus Nucleocapsid Protein Directs Basal Endothelial Cell Permeability by Activating RhoA.mBio · 2016Article
- Positive regulation of Rho GTPase activity by RhoGDIs as a result of their direct interaction with GAPs.BMC systems biology · 2015Article
- Cytoskeletal mechanisms regulating vascular endothelial barrier function in response to acute lung injury.Tissue barriers · 2015Article
- Mechanisms regulating endothelial permeability.Pulmonary circulation · 2014Review
- Ezrin/radixin/moesin proteins differentially regulate endothelial hyperpermeability after thrombin.American journal of physiology. Lung cellular and molecular physiology · 2013Article
- Neural Wiskott-Aldrich syndrome protein (N-WASP)-mediated p120-catenin interaction with Arp2-Actin complex stabilizes endothelial adherens junctions.The Journal of biological chemistry · 2013Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
We identified the GDI-1-regulated mechanism of RhoA activation from the Rho-GDI-1 complex and its role in mediating increased endothelial permeability. Thrombin stimulation failed to induce RhoA activation and actin stress fiber formation in human pulmonary arterial endothelial cells transduced with full-length GDI-1. Expression of a GDI-1 mutant form (C-GDI) containing the C terminus (aa 69 to 204) also prevented RhoA activation, whereas further deletions failed to alter RhoA activation. We observed that protein kinase Calpha-mediated phosphorylation of the C terminus of GDI-1 at Ser96 reduced the affinity of GDI-1 for RhoA and thereby enabled RhoA activation. Rendering GDI-1 phosphodefective with a Ser96 --> Ala substitution rescued the inhibitory activity of GDI-1 toward RhoA but did not alter the thrombin-induced activation of other Rho GTPases, i.e., Rac1 and Cdc42. Phosphodefective mutant GDI-1 also suppressed myosin light chain phosphorylation, actin stress fiber formation, and the increased endothelial permeability induced by thrombin. In contrast, expressing the phospho-mimicking mutant S96D-GDI-1 protein induced RhoA activity and increased endothelial permeability independently of thrombin stimulation. These results demonstrate the crucial role of the phosphorylation of the C terminus of GDI-1 at S96 in selectively activating RhoA. Inhibiting GDI-1 phosphorylation at S96 is a potential therapeutic target for modulating RhoA activity and thus preventing the increase in endothelial permeability associated with vascular inflammation.
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