ArticleThe Journal of biological chemistry2016
Enzyme Activities of the Ceramide Synthases CERS2-6 Are Regulated by Phosphorylation in the C-terminal Region.
Article in The Journal of biological chemistry, 2016. 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, 84 citations in OpenAlex.
- CerS2-mediated lipotoxicity and calcium signaling: a novel sequential mechanism of apoptosis in cancer.The Biochemical journal · 2026Review
- Structural and functional dissection of a higher-order oligomerization interface in yeast ceramide synthase.Nature communications · 2026Article
- The Role of Ceramides in Metabolic and Cardiovascular Diseases.Journal of cardiovascular development and disease · 2026Review
- [Effect of dephosphorylation of tumor metastasis suppressor geneBeijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2025Article
- Ceramide Synthase 2 Promotes Cardiac Very-Long-Chain Dihydroceramide Accumulation and Is Linked to Arrhythmias and Heart Failure in Humans.International journal of molecular sciences · 2025Article
- Relationship between time-dependent epidermal ceramide composition changes and skin barrier function in adult mice.Molecular biology of the cell · 2025Article
- Structural basis of the mechanism and inhibition of a human ceramide synthase.Nature structural & molecular biology · 2025Article
- Neurotensin-neurotensin receptor 2 signaling in adipocytes suppresses food intake through regulating ceramide metabolism.Cell research · 2025Article
- Sphingolipid metabolism and regulated cell death in malignant melanoma.Apoptosis : an international journal on programmed cell death · 2024Review
- How ceramides affect the development of colon cancer: from normal colon to carcinoma.Pflugers Archiv : European journal of physiology · 2024Review
- Unravelling neuronal and glial differences in ceramide composition, synthesis, and sensitivity to toxicity.Communications biology · 2024Article
- Glycosphingolipids: from metabolism to chemoenzymatic total synthesis.Organic & biomolecular chemistry · 2024Review
- GIMAP5 deficiency reveals a mammalian ceramide-driven longevity assurance pathway.Nature immunology · 2024Article
- LASS2 enhances chemosensitivity to cisplatin by inhibiting PP2A-mediated β-catenin dephosphorylation in a subset of stem-like bladder cancer cells.BMC medicine · 2024Article
- Structure and mechanism of a eukaryotic ceramide synthase complex.The EMBO journal · 2023Article
- The Implication of Sphingolipids in Viral Infections.International journal of molecular sciences · 2023Review
- Cholesterol-dependent homeostatic regulation of very long chain sphingolipid synthesis.The Journal of cell biology · 2023Article
- The Ying and Yang of Ganglioside Function in Cancer.Cancers · 2023Review
- Toxoplasma ceramide synthases: Gene duplication, functional divergence, and roles in parasite fitness.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- The heat shock protein Hsp27 controls mitochondrial function by modulating ceramide generation.Cell reports · 2023Article
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Authors and funding
3 authors at 1 institution in 1 country.
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Abstract
Ceramide and complex sphingolipids regulate important cellular functions including cell growth, apoptosis, and signaling. Dysregulation of sphingolipid metabolism leads to pathological consequences such as sphingolipidoses and insulin resistance. Ceramides in mammals vary greatly in their acyl-chain composition: six different ceramide synthase isozymes (CERS1-6) that exhibit distinct substrate specificity and tissue distribution account for this diversity. In the present study, we demonstrated that CERS2-6 were phosphorylated at the cytoplasmic C-terminal regions. Most of the phosphorylated residues conformed to a consensus motif for phosphorylation by casein kinase 2 (CK2), and treatment of cells with the CK2-specific inhibitor CX-4945 lowered the phosphorylation levels of CERS2, -4, -5, and -6. Phosphorylation of CERS2 was especially important for its catalytic activity, acting mainly by increasing itsVmaxvalue. Phosphorylation modestly increased the catalytic activities of CERS4 and -5 and mildly increased those of CERS3 and -6. Dephosphorylation of endogenous ceramide synthases in the mouse brain led to severely reduced activity toward the Cers2 substrates C22:0/C24:0-CoAs and modestly reduced activity toward the Cers5/6 substrate C16:0-CoA. These results suggest that the phosphorylation of ceramide synthases may be a key regulatory point in the control of the distribution and levels of sphingolipids of various acyl-chain lengths.
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