ArticleCellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology2009
A ceramide-binding C1 domain mediates kinase suppressor of ras membrane translocation.
Article in Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 2009. 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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Who cites it
35 citing papers in PubMed, 50 citations in OpenAlex.
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- Review
- Cancer progression through the lens of age-induced metabolic reprogramming.Nature reviews. Cancer · 2025Review
- Development of Genetically Encoded Fluorescent KSR1-Based Probes to Track Ceramides during Phagocytosis.International journal of molecular sciences · 2024Article
- 1,3-Dichloroadamantyl-Containing Ureas as Potential Triple Inhibitors of Soluble Epoxide Hydrolase, p38 MAPK and c-Raf.International journal of molecular sciences · 2023Article
- Navigating the ERK1/2 MAPK Cascade.Biomolecules · 2023Review
- KSR induces RAS-independent MAPK pathway activation and modulates the efficacy of KRAS inhibitors.Molecular oncology · 2022Article
- Lipid alterations in chronic liver disease and liver cancer.JHEP reports : innovation in hepatology · 2022Review
- Ceramide regulates interaction of Hsd17b4 with Pex5 and function of peroxisomes.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2019Article
- Mechanism of Rapid Nuclear Factor-E2-Related Factor 2 (Nrf2) Activation via Membrane-Associated Estrogen Receptors: Roles of NADPH Oxidase 1, Neutral Sphingomyelinase 2 and Epidermal Growth Factor Receptor (EGFR).Antioxidants (Basel, Switzerland) · 2019Review
- Quantitative biophysical analysis defines key components modulating recruitment of the GTPase KRAS to the plasma membrane.The Journal of biological chemistry · 2019Article
- Insulin-stimulated Rac1-GTP binding is not impaired by palmitate treatment in L6 myotubes.Physiological reports · 2018Article
- Visualizing bioactive ceramides.Chemistry and physics of lipids · 2018Review
- CNature communications · 2018Article
- Ceramide Signaling and p53 Pathways.Advances in cancer research · 2018Review
- Sphingolipid abnormalities in cancer multidrug resistance: Chicken or egg?Cellular signalling · 2017Review
- Proteome-wide Identification of Novel Ceramide-binding Proteins by Yeast Surface cDNA Display and Deep Sequencing.Molecular & cellular proteomics : MCP · 2016Article
- Laurdan monitors different lipids content in eukaryotic membrane during embryonic neural development.Cell biochemistry and biophysics · 2014Article
- Re-configuration of sphingolipid metabolism by oncogenic transformation.Biomolecules · 2014Review
- Membrane signaling induced by high doses of ionizing radiation in the endothelial compartment. Relevance in radiation toxicity.International journal of molecular sciences · 2013Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Genetic and biochemical data support Kinase Suppressor of Ras 1 (KSR1) as a positive regulator of the Ras-Raf-MAPK pathway, functioning as a kinase and/or scaffold to regulate c-Raf-1 activation. Membrane translocation mediated by the KSR1 CA3 domain, which is homologous to the atypical PKC C1 lipid-binding domain, is a critical step of KSR1-mediated c-Raf-1 activation. In this study, we used an ELISA to characterize the KSR1 CA3 domain as a lipid-binding moiety. Purified GST-KSR1-CA3 protein effectively binds ceramide but not other lipids including 1,2-diacylglyceol, dihydroceramide, ganglioside GM1, sphingomyelin and phosphatidylcholine. Upon epidermal growth factor stimulation of COS-7 cells, KSR1 translocates into and is activated within glycosphingolipid-enriched plasma membrane platforms. Pharmacologic inhibition of ceramide generation attenuates KSR1 translocation and KSR1 kinase activation in COS-7 cells. Disruption of two cysteines, which are indispensable for maintaining ternary structure of all C1 domains and their lipid binding capability, mitigates ceramide-binding capacity of purified GST-KSR1-CA3 protein, and inhibits full length KSR1 membrane translocation and kinase activation. These studies provide evidence for a mechanism by which the second messenger ceramide can target proteins to subcellular compartments in the process of transmembrane signal transduction.
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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.