ArticleScience signaling2013
The ζ isoform of diacylglycerol kinase plays a predominant role in regulatory T cell development and TCR-mediated ras signaling.
Article in Science signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 69 citations in OpenAlex.
- Article
- Deciphering protein mutation-phenotype linkages from CRISPR-based tiling mutagenesis screens.Cell systems · 2026Article
- Modulators of Diacylglycerol Kinase Activity: A Review of Advances and Challenges.Medicinal research reviews · 2026Review
- CRISPR-Cas9 knockout of DGKα/ζ improves the anti-tumor activities of TAG-72 CAR-T cells in ovarian cancer.Molecular therapy. Oncology · 2025Article
- Accelerating CAR-T Cell Therapies with Small-Molecule Inhibitors.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2025Review
- Diacylglycerol kinase is a keystone regulator of signaling relevant to the pathophysiology of asthma.American journal of physiology. Lung cellular and molecular physiology · 2024Review
- DGKα/ζ inhibition lowers the TCR affinity threshold and potentiates antitumor immunity.Science advances · 2023Article
- Wiskott-Aldrich syndrome protein interacts and inhibits diacylglycerol kinase alpha promoting IL-2 induction.Frontiers in immunology · 2023Article
- Mutations of RAS genes identified in acute myeloid leukemia affect glycerophospholipid metabolism pathway.Frontiers in oncology · 2023Article
- T-helper cells flexibility: the possibility of reprogramming T cells fate.Frontiers in immunology · 2023Review
- Regulation of Airway Smooth Muscle Cell Proliferation by Diacylglycerol Kinase: Relevance to Airway Remodeling in Asthma.International journal of molecular sciences · 2022Article
- Identification of ritanserin analogs that display DGK isoform specificity.Biochemical pharmacology · 2022Article
- Manipulation of diacylglycerol and ERK-mediated signaling differentially controls CD8Frontiers in immunology · 2022Article
- Advances in chemical proteomic evaluation of lipid kinases-DAG kinases as a case study.Current opinion in chemical biology · 2021Review
- Diacylglycerol Kinase alpha in X Linked Lymphoproliferative Disease Type 1.International journal of molecular sciences · 2021Review
- Review
- DGKζ exerts greater control than DGKα over CD8Oncoimmunology · 2021Article
- Structure activity relationship studies on Amb639752: toward the identification of a common pharmacophoric structure for DGKα inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2020Article
- Negative control of diacylglycerol kinase ζ-mediated inhibition of T cell receptor signaling by nuclear sequestration in mice.European journal of immunology · 2020Article
- Interplay Between SNX27 and DAG Metabolism in the Control of Trafficking and Signaling at the IS.International journal of molecular sciences · 2020Review
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Diacylglycerol (DAG) is a critical second messenger that mediates T cell receptor (TCR)-stimulated signaling. The abundance of DAG is reduced by the diacylglycerol kinases (DGKs), which catalyze the conversion of DAG to phosphatidic acid (PA) and thus inhibit DAG-mediated signaling. In T cells, the predominant DGK isoforms are DGKα and DGKζ, and deletion of the genes encoding either isoform enhances DAG-mediated signaling. We found that DGKζ, but not DGKα, suppressed the development of natural regulatory T (T(reg)) cells and predominantly mediated Ras and Akt signaling downstream of the TCR. The differential functions of DGKα and DGKζ were not attributable to differences in protein abundance in T cells or in their localization to the contact sites between T cells and antigen-presenting cells. RasGRP1, a key DAG-mediated activator of Ras signaling, associated to a greater extent with DGKζ than with DGKα; however, in silico modeling of TCR-stimulated Ras activation suggested that a difference in RasGRP1 binding affinity was not sufficient to cause differences in the functions of each DGK isoform. Rather, the model suggested that a greater catalytic rate for DGKζ than for DGKα might lead to DGKζ exhibiting increased suppression of Ras-mediated signals compared to DGKα. Consistent with this notion, experimental studies demonstrated that DGKζ was more effective than DGKα at catalyzing the metabolism of DAG to PA after TCR stimulation. The enhanced effective enzymatic production of PA by DGKζ is therefore one possible mechanism underlying the dominant functions of DGKζ in modulating T(reg) cell development.
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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.