ArticleThe Journal of biological chemistry2010
Neutral sphingomyelinase 2 (nSMase2) is a phosphoprotein regulated by calcineurin (PP2B).
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 60 citations in OpenAlex.
- Electrical Stimulation-Induced Modulation of Small Extracellular Vesicles in Regenerative Therapy.Tissue engineering and regenerative medicine · 2026Review
- Estrogen Influences Human Microvascular Endothelial Function Via Sex-Specific Regulation of Sphingolipids.JACC. Basic to translational science · 2026Article
- Glucocorticoids regulate small extracellular vesicle (sEV) release via activation of nSMase2.bioRxiv : the preprint server for biology · 2025Article
- Neutral sphingomyelinase 2: A promising drug target for CNS disease.Advances in pharmacology (San Diego, Calif.) · 2025Review
- Dynamic changes in the proximitome of neutral sphingomyelinase-2 (nSMase2) in TNFα stimulated Jurkat cells.Frontiers in immunology · 2024Article
- Inhibition of neutral sphingomyelinase 2 impairs HIV-1 envelope formation and substantially delays or eliminates viral rebound.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Neutral sphingomyelinase-2 and cardiometabolic diseases.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2021Review
- Sphingomyelinases and Liver Diseases.Biomolecules · 2020Review
- Protein Binding and Stability of Drug Candidates: The Achilles' Heel in In Vitro Potency Assays.European journal of drug metabolism and pharmacokinetics · 2020Article
- Review
- Article
- Synaptic vesicle generation from activity-dependent bulk endosomes requires a dephosphorylation-dependent dynamin-syndapin interaction.Journal of neurochemistry · 2019Article
- The juxtamembrane linker in neutral sphingomyelinase-2 functions as an intramolecular allosteric switch that activates the enzyme.The Journal of biological chemistry · 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
- Neutral Sphingomyelinase Inhibition Alleviates LPS-Induced Microglia Activation and Neuroinflammation after Experimental Traumatic Brain Injury.The Journal of pharmacology and experimental therapeutics · 2019Article
- 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
- Role of Neutral Sphingomyelinase-2 (NSM 2) in the Control of T Cell Plasma Membrane Lipid Composition and Cholesterol Homeostasis.Frontiers in cell and developmental biology · 2019Article
- Structure of human nSMase2 reveals an interdomain allosteric activation mechanism for ceramide generation.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- ATRA transcriptionally induces nSMase2 through CBP/p300-mediated histone acetylation.Journal of lipid research · 2016Article
- The hyaluronic acid inhibitor 4-methylumbelliferone is an NSMase2 activator-role of Ceramide in MU anti-tumor activity.Biochimica et biophysica acta · 2016Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
We previously reported that exposure of human airway epithelial cells to oxidative stress increased ceramide generation via specific activation of neutral sphingomyelinase2 (nSMase2). Here we show that nSMase2 is a phosphoprotein exclusively phosphorylated at serine residues. The level of nSMase2 phosphorylation can be modulated by treatment with anisomycin or phorbol 12-myristate 13-acetate (PMA/12-O-tetradecanoylphorbol-13-acetate), suggesting that p38 mitogen-activated protein kinase (MAPK) and protein kinases Cs are upstream of nSMase2 phosphorylation. Oxidative stress enhances both the activity and phosphorylation of nSMase2. Strikingly, we show here that nSMase2 is bound directly by the phosphatase calcineurin (CaN), which acts as an on/off switch for nSMase2 phosphorylation in the presence or absence of oxidative stress. Specifically, CaN is being inhibited/degraded and therefore does not bind nSMase2 under oxidative stress, and a mutant nSMase2 that lacks the CaN binding site exhibits constitutively elevated phosphorylation and increased activity relative to wild type nSMase2. Importantly, the phosphorylation and activity of the mutant no longer responds to oxidative stress, confirming that CaN is the critical link that allows oxidative stress to modulate nSMase2 phosphorylation and function.
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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.