ArticleThe Journal of biological chemistry2012
Staurosporines disrupt phosphatidylserine trafficking and mislocalize Ras proteins.
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 65 papers.
What it found
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Who cites it
65 citing papers in PubMed.
- Apical and basolateral plasma membranes in epithelial cells have distinct lipidomes and biophysical properties.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Targeting KRAS mutations: orchestrating cancer evolution and therapeutic challenges.Signal transduction and targeted therapy · 2025Review
- Apical and basolateral plasma membranes in epithelial cells have distinct lipidomes and biophysical properties.bioRxiv : the preprint server for biology · 2025Article
- MTMR regulates KRAS function by controlling plasma membrane levels of phospholipids.The Journal of cell biology · 2025Article
- Evaluation of fendiline treatment in VP40 system with nucleation-elongation process: a computational model of Ebola virus matrix protein assembly.Microbiology spectrum · 2024Article
- A new ferrocene derivative blocks K-Ras localization and function by oxidative modification at His95.Life science alliance · 2023Article
- Article
- The phospholipid transporter PITPNC1 links KRAS to MYC to prevent autophagy in lung and pancreatic cancer.Molecular cancer · 2023Article
- RAS nanoclusters are cell surface transducers that convert extracellular stimuli to intracellular signalling.FEBS letters · 2023Review
- Characterizations of annexin A1-interacting proteins in apical membrane and cytosolic compartments of renal tubular epithelial cells.Computational and structural biotechnology journal · 2023Article
- Mechanisms of phosphatidylserine influence on viral production: A computational model of Ebola virus matrix protein assembly.The Journal of biological chemistry · 2022Article
- Past and Future Strategies to Inhibit Membrane Localization of the KRAS Oncogene.International journal of molecular sciences · 2021Review
- Lipid Profiles of RAS Nanoclusters Regulate RAS Function.Biomolecules · 2021Review
- Approaches to inhibiting oncogenic K-Ras.Small GTPases · 2021Review
- 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
- Blocking K-Ras Interaction With the Plasma Membrane Is a Tractable Therapeutic Approach to Inhibit Oncogenic K-Ras Activity.Frontiers in molecular biosciences · 2021Review
- Ras Variant Biology and Contributions to Human Disease.Methods in molecular biology (Clifton, N.J.) · 2021Review
- RAS Nanoclusters Selectively Sort Distinct Lipid Headgroups and Acyl Chains.Frontiers in molecular biosciences · 2021Review
- RAS Function in cancer cells: translating membrane biology and biochemistry into new therapeutics.The Biochemical journal · 2020Review
- Avicin G is a potent sphingomyelinase inhibitor and blocks oncogenic K- and H-Ras signaling.Scientific reports · 2020Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Oncogenic mutant Ras is frequently expressed in human cancers, but no anti-Ras drugs have been developed. Since membrane association is essential for Ras biological activity, we developed a high content assay for inhibitors of Ras plasma membrane localization. We discovered that staurosporine and analogs potently inhibit Ras plasma membrane binding by blocking endosomal recycling of phosphatidylserine, resulting in redistribution of phosphatidylserine from plasma membrane to endomembrane. Staurosporines are more active against K-Ras than H-Ras. K-Ras is displaced to endosomes and undergoes proteasomal-independent degradation, whereas H-Ras redistributes to the Golgi and is not degraded. K-Ras nanoclustering on the plasma membrane is also inhibited. Ras mislocalization does not correlate with protein kinase C inhibition or induction of apoptosis. Staurosporines selectively abrogate K-Ras signaling and proliferation of K-Ras-transformed cells. These results identify staurosporines as novel inhibitors of phosphatidylserine trafficking, yield new insights into the role of phosphatidylserine and electrostatics in Ras plasma membrane targeting, and validate a new target for anti-Ras therapeutics.
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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.