ArticleMolecular biology of the cell2009
Casein kinase I{gamma}2 down-regulates trafficking of ceramide in the synthesis of sphingomyelin.
Article in Molecular biology of the cell, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 61 citations in OpenAlex.
- Emerging roles of lipid transfer protein dimerization.Journal of cell science · 2025Review
- The C10orf76-PI4KB axis orchestrates CERT-mediated ceramide trafficking to the distal Golgi.The Journal of cell biology · 2023Article
- CERT1 mutations perturb human development by disrupting sphingolipid homeostasis.The Journal of clinical investigation · 2023Article
- Casein kinase 1α mediates eryptosis: a review.Apoptosis : an international journal on programmed cell death · 2023Review
- Involvement of a Cluster of Basic Amino Acids in Phosphorylation-Dependent Functional Repression of the Ceramide Transport Protein CERT.International journal of molecular sciences · 2022Article
- Compartmentalization of casein kinase 1 γ CSNK1G controls the intracellular trafficking of ceramide.iScience · 2022Article
- Hyperosmotic Stress Induces Phosphorylation of CERT and Enhances Its Tethering throughout the Endoplasmic Reticulum.International journal of molecular sciences · 2022Article
- Natural Ligand-Mimetic and Nonmimetic Inhibitors of the Ceramide Transport Protein CERT.International journal of molecular sciences · 2022Review
- Ceramide Transfer Protein (CERT): An Overlooked Molecular Player in Cancer.International journal of molecular sciences · 2021Review
- Sphingolipid-Transporting Proteins as Cancer Therapeutic Targets.International journal of molecular sciences · 2019Review
- Lipid transfer proteins rectify inter-organelle flux and accurately deliver lipids at membrane contact sites.Journal of lipid research · 2018Review
- Phosphoinositide binding by the PH domain in ceramide transfer protein (CERT) is inhibited by hyperphosphorylation of an adjacent serine-repeat motif.The Journal of biological chemistry · 2018Article
- Interaction between the PH and START domains of ceramide transfer protein competes with phosphatidylinositol 4-phosphate binding by the PH domain.The Journal of biological chemistry · 2017Article
- Dihydroceramide accumulation mediates cytotoxic autophagy of cancer cells via autolysosome destabilization.Autophagy · 2016Article
- RPTOR, a novel target of miR-155, elicits a fibrotic phenotype of cystic fibrosis lung epithelium by upregulating CTGF.RNA biology · 2016Article
- Establishment of Par-Polarized Cortical Domains via Phosphoregulated Membrane Motifs.Developmental cell · 2015Article
- A computational model of PKD and CERT interactions at the trans-Golgi network of mammalian cells.BMC systems biology · 2015Article
- Phosphoregulation of the ceramide transport protein CERT at serine 315 in the interaction with VAMP-associated protein (VAP) for inter-organelle trafficking of ceramide in mammalian cells.The Journal of biological chemistry · 2014Article
- Alternation in the glycolipid transfer protein expression causes changes in the cellular lipidome.PloS one · 2014Article
- The CK1 Family: Contribution to Cellular Stress Response and Its Role in Carcinogenesis.Frontiers in oncology · 2014Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intracellullar trafficking of lipids is fundamental to membrane biogenesis. For the synthesis of sphingomyelin, ceramide is transported from the endoplasmic reticulum to the Golgi apparatus by the ceramide transfer protein CERT. CERT is phosphorylated by protein kinase D at S132 and subsequently multiple times in a serine-repeat motif, resulting in its inactivation. However, the kinase involved in the multiple phosphorylation remains unclear. Here, we identify the gamma2 isoform of casein kinase I (CKIgamma2) as a kinase whose overexpression confers sphingomyelin-directed toxin-resistance to Chinese hamster ovary cells. In a transformant stably expressing CKIgamma2, CERT was hyperphosphorylated, and the intracellular trafficking of ceramide was retarded, thereby reducing de novo sphingomyelin synthesis. The reduction in the synthesis of sphingomyelin caused by CKIgamma2 was reversed by the expression of CERT mutants that are not hyperphosphorylated. Furthermore, CKIgamma2 directly phosphorylated CERT in vitro. Among three gamma isoforms, only knockdown of gamma2 isoform caused drastic changes in the ratio of hypo- to hyperphosphorylated form of CERT in HeLa cells. These results indicate that CKIgamma2 hyperphosphorylates the serine-repeat motif of CERT, thereby inactivating CERT and down-regulating the synthesis of sphingomyelin.
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