ArticleThe Journal of biological chemistry2012
Nonsteroidal anti-inflammatory drugs alter the spatiotemporal organization of Ras proteins on the plasma membrane.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
35 citing papers in PubMed, 60 citations in OpenAlex.
- Lipid Raft Membrane Interactivity Correlating with Cyclooxygenase-2 Selectivity of Non-Steroidal Anti-Inflammatory Drugs.Membranes · 2025Article
- Molecular docking as a tool for the discovery of novel insight about the role of acid sphingomyelinase inhibitors in SARS- CoV-2 infectivity.BMC public health · 2024Review
- RAS nanoclusters are cell surface transducers that convert extracellular stimuli to intracellular signalling.FEBS letters · 2023Review
- Remodeling of the Plasma Membrane by Surface-Bound Protein Monomers and Oligomers: The Critical Role of Intrinsically Disordered Regions.The Journal of membrane biology · 2022Review
- High-Content Imaging Platform to Discover Chemical Modulators of Plasma Membrane Rafts.ACS central science · 2022Article
- Elaiophylin Is a Potent Hsp90/ Cdc37 Protein Interface Inhibitor with K-Ras Nanocluster Selectivity.Biomolecules · 2021Article
- The KRAS and other prenylated polybasic domain membrane anchors recognize phosphatidylserine acyl chain structure.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Super-Resolution Imaging and Spatial Analysis of RAS on Intact Plasma Membrane Sheets.Methods in molecular biology (Clifton, N.J.) · 2021Article
- RAS Nanoclusters Selectively Sort Distinct Lipid Headgroups and Acyl Chains.Frontiers in molecular biosciences · 2021Review
- Impact of Plasma Membrane Domains on IgG Fc Receptor Function.Frontiers in immunology · 2020Review
- Review
- Formation of Drug-Participating Catanionic Aggregates for Extended Delivery of Non-Steroidal Anti-Inflammatory Drugs from Contact Lenses.Biomolecules · 2019Article
- Omega-3 fatty acids, membrane remodeling and cancer prevention.Molecular aspects of medicine · 2018Review
- Functional link between plasma membrane spatiotemporal dynamics, cancer biology, and dietary membrane-altering agents.Cancer metastasis reviews · 2018Review
- Long-Chain n-3 Fatty Acids Attenuate Oncogenic KRas-Driven Proliferation by Altering Plasma Membrane Nanoscale Proteolipid Composition.Cancer research · 2018Article
- Deciphering lipid codes: K-Ras as a paradigm.Traffic (Copenhagen, Denmark) · 2018Review
- Aspirin locally disrupts the liquid-ordered phase.Royal Society open science · 2018Article
- Electron microscopy combined with spatial analysis: quantitative mapping of the nano-assemblies of plasma membrane-associating proteins and lipids.Biophysics reports · 2018Article
- Emerging role of chemoprotective agents in the dynamic shaping of plasma membrane organization.Biochimica et biophysica acta. Biomembranes · 2017Review
- Calmodulin and PI3K Signaling inTrends in cancer · 2017Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Ras proteins on the inner leaflet of the plasma membrane signal from transient nanoscale proteolipid assemblies called nanoclusters. Interactions between the Ras lipid anchors and plasma membrane phospholipids, cholesterol, and actin cytoskeleton contribute to the formation, stability, and dynamics of Ras nanoclusters. Many small biological molecules are amphiphilic and capable of intercalating into membranes and altering lipid immiscibility. In this study we systematically examined whether amphiphiles such as indomethacin influence Ras protein nanoclustering in intact plasma membrane. We found that indomethacin, a nonsteroidal anti-inflammatory drug, induced profound and complex effects on Ras spatial organization, all likely related to liquid-ordered domain stabilization. Indomethacin enhanced the clustering of H-Ras.GDP and N-Ras.GTP in cholesterol-dependent nanoclusters. Indomethacin also abrogated efficient GTP-dependent lateral segregation of H- and N-Ras between cholesterol-dependent and cholesterol-independent clusters, resulting in mixed heterotypic clusters of Ras proteins that normally are separated spatially. These heterotypic Ras nanoclusters showed impaired Raf recruitment and kinase activation resulting in significantly compromised MAPK signaling. All of the amphiphilic anti-inflammatory agents we tested had similar effects on Ras nanoclustering and signaling. The potency of these effects correlated with the membrane partition coefficients of the individual agents and was independent of COX inhibition. This study shows that biological amphiphiles have wide-ranging effects on plasma membrane heterogeneity and protein nanoclustering, revealing a novel mechanism of drug action that has important consequences for cell signaling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.