ArticleProceedings of the National Academy of Sciences of the United States of America1999
Stimulation of CD95 (Fas) blocks T lymphocyte calcium channels through sphingomyelinase and sphingolipids.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 177 citations in OpenAlex.
- The Acid sphingomyelinase/ceramide System in Idiopathic Inflammatory Myopathies: a Potential Treatment Target.Inflammation · 2026Review
- Metabolic-immune crosstalk in osteosarcoma: mechanisms and therapeutic opportunities.Frontiers in immunology · 2026Review
- Ceramide signaling in immunity: a molecular perspective.Lipids in health and disease · 2025Review
- Multi-omic validation of the cuproptosis-sphingolipid metabolism network: modulating the immune landscape in osteosarcoma.Frontiers in immunology · 2024Article
- Sphingolipids in thyroid eye disease.Frontiers in endocrinology · 2023Review
- The Role of NLRP3 Inflammasome in Radiation-Induced Cardiovascular Injury.Frontiers in cell and developmental biology · 2020Review
- Sphingomyelin Breakdown in T Cells: Role of Membrane Compartmentalization in T Cell Signaling and Interference by a Pathogen.Frontiers in cell and developmental biology · 2019Review
- The Neutral Sphingomyelinase 2 Is Required to Polarize and Sustain T Cell Receptor Signaling.Frontiers in immunology · 2018Article
- Regulation of endothelial Fas expression as a mechanism of promotion of vascular integrity by mural cells in tumors.Cancer science · 2017Article
- Microbial sphingomyelinase induces RhoA-mediated reorganization of the apical brush border membrane and is protective against invasion.Molecular biology of the cell · 2016Article
- Sphingomyelinase D inhibits store-operated Ca2+ entry in T lymphocytes by suppressing ORAI current.The Journal of general physiology · 2015Article
- Role of acid sphingomyelinase bioactivity in human CD4+ T-cell activation and immune responses.Cell death & disease · 2015Article
- Pseudomonas aeruginosa pyocyanin induces neutrophil death via mitochondrial reactive oxygen species and mitochondrial acid sphingomyelinase.Antioxidants & redox signaling · 2015Article
- Neutral sphingomyelinase in physiological and measles virus induced T cell suppression.PLoS pathogens · 2014Article
- Exploring the link between ceramide and ionizing radiation.Glycoconjugate journal · 2014Review
- Membrane signaling induced by high doses of ionizing radiation in the endothelial compartment. Relevance in radiation toxicity.International journal of molecular sciences · 2013Review
- Life in the Fas lane: differential outcomes of Fas signaling.Cellular and molecular life sciences : CMLS · 2013Review
- Acid sphingomyelinase-ceramide system mediates effects of antidepressant drugs.Nature medicine · 2013Article
- Regulation of de novo ceramide synthesis: the role of dihydroceramide desaturase and transcriptional factors NFATC and Hand2 in the hypoxic mouse heart.DNA and cell biology · 2013Article
- Complexation of c6-ceramide with cholesteryl phosphocholine - a potent solvent-free ceramide delivery formulation for cells in culture.PloS one · 2013Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Calcium influx through store-operated calcium release-activated calcium channels (CRAC) is required for T cell activation, cytokine synthesis, and proliferation. The CD95 (Apo-1/Fas) receptor plays a role in self-tolerance and tumor immune escape, and it mediates apoptosis in activated T cells. In this paper we show that CD95-stimulation blocks CRAC and Ca(2+) influx in lymphocytes through the activation of acidic sphingomyelinase (ASM) and ceramide release. The block of Ca(2+) entry is lacking in CD95-defective lpr lymphocytes as well as in ASM-defective cells and can be restored by retransfection of ASM. C2 ceramide, C6 ceramide, and sphingosine block CRAC reversibly, whereas the inactive dihydroceramide has no effect. CD95-stimulation or the addition of ceramide prevents store-operated Ca(2+) influx, activation of the transcriptional regulator NFAT, and IL-2 synthesis. The block of CRAC by sphingomyelinase metabolites adds a function to the repertoire of the CD95 receptor inhibiting T cell activation signals.
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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.