ArticleMolecular and cellular biology2012
FoxO-dependent regulation of diacylglycerol kinase α gene expression.
Article in Molecular and cellular biology, 2012. 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, 34 citations in OpenAlex.
- Diacylglycerol kinase-ε is required for the formation of GPI-anchored CD14 and the LPS-induced proinflammatory responses of macrophages.Cell communication and signaling : CCS · 2026Article
- Modulators of Diacylglycerol Kinase Activity: A Review of Advances and Challenges.Medicinal research reviews · 2026Review
- DGKs in lipid signaling and disease intervention: structural basis, pathological mechanisms, and emerging therapeutic strategies.Cellular & molecular biology letters · 2025Review
- Wiskott-Aldrich syndrome protein interacts and inhibits diacylglycerol kinase alpha promoting IL-2 induction.Frontiers in immunology · 2023Article
- Overarching roles of diacylglycerol signaling in cancer development and antitumor immunity.Science signaling · 2022Review
- Immune Checkpoint Receptors Signaling in T Cells.International journal of molecular sciences · 2022Review
- The expression of diacylglycerol kinase isoforms α and ζ correlates with the progression of experimental autoimmune encephalomyelitis in rats.Histochemistry and cell biology · 2021Article
- Diacylglycerol kinase α inhibition cooperates with PD-1-targeted therapies to restore the T cell activation program.Cancer immunology, immunotherapy : CII · 2021Article
- Negative control of diacylglycerol kinase ζ-mediated inhibition of T cell receptor signaling by nuclear sequestration in mice.European journal of immunology · 2020Article
- Diacylglycerol kinase ζ limits IL-2-dependent control of PD-1 expression in tumor-infiltrating T lymphocytes.Journal for immunotherapy of cancer · 2020Article
- Beyond Lipid Signaling: Pleiotropic Effects of Diacylglycerol Kinases in Cellular Signaling.International journal of molecular sciences · 2020Review
- Subcellular Localization Relevance and Cancer-Associated Mechanisms of Diacylglycerol Kinases.International journal of molecular sciences · 2020Review
- Graded diacylglycerol kinases α and ζ activities ensure mucosal-associated invariant T-cell development in mice.European journal of immunology · 2020Article
- Diacylglycerol Kinase Alpha in Radiation-Induced Fibrosis: Potential as a Predictive Marker or Therapeutic Target.Frontiers in oncology · 2020Review
- Beyond the Cell Surface: Targeting Intracellular Negative Regulators to Enhance T cell Anti-Tumor Activity.International journal of molecular sciences · 2019Review
- DGKα in Neutrophil Biology and Its Implications for Respiratory Diseases.International journal of molecular sciences · 2019Review
- Diacylglycerol kinase α inactivation is an integral component of the costimulatory pathway that amplifies TCR signals.Cancer immunology, immunotherapy : CII · 2018Article
- Diacylglycerol kinase α deficiency alters inflammation markers in adipose tissue in response to a high-fat diet.Journal of lipid research · 2018Article
- Predominant contribution of DGKζ over DGKα in the control of PKC/PDK-1-regulated functions in T cells.Immunology and cell biology · 2017Article
- DGK-α: A Checkpoint in Cancer-Mediated Immuno-Inhibition and Target for Immunotherapy.Frontiers in cell and developmental biology · 2017Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Diacylglycerol kinase α (DGKα) regulates diacylglycerol levels, catalyzing its conversion into phosphatidic acid. The α isoform is central to immune response regulation; it downmodulates Ras-dependent pathways and is necessary for establishment of the unresponsive state termed anergy. DGKα functions are regulated in part at the transcriptional level although the mechanisms involved remain poorly understood. Here, we analyzed the 5' end structure of the mouse DGKα gene and detected three binding sites for forkhead box O (FoxO) transcription factors, whose function was confirmed using luciferase reporter constructs. FoxO1 and FoxO3 bound to the 5' regulatory region of DGKα in quiescent T cells, as well as after interleukin-2 (IL-2) withdrawal in activated T cells. FoxO binding to this region was lost after complete T cell activation or IL-2 addition, events that correlated with FoxO phosphorylation and a sustained decrease in DGKα gene expression. These data strongly support a role for FoxO proteins in promoting high DGKα levels and indicate a mechanism by which DGKα function is downregulated during productive T cell responses. Our study establishes a basis for a causal relationship between DGKα downregulation, IL-2, and anergy avoidance.
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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 Socratic graph.