ArticleImmunology and cell biology2017
Predominant contribution of DGKζ over DGKα in the control of PKC/PDK-1-regulated functions in T cells.
Article in Immunology and cell biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 29 citations in OpenAlex.
- Modulators of Diacylglycerol Kinase Activity: A Review of Advances and Challenges.Medicinal research reviews · 2026Review
- 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
- Review
- Immune Checkpoint Receptors Signaling in T Cells.International journal of molecular sciences · 2022Review
- Article
- 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
- Diacylglycerol Kinase alpha in X Linked Lymphoproliferative Disease Type 1.International journal of molecular sciences · 2021Review
- Sorting Nexin 27 Enables MTOC and Secretory Machinery Translocation to the Immune Synapse.Frontiers in immunology · 2021Article
- Diacylglycerol kinase ζ limits IL-2-dependent control of PD-1 expression in tumor-infiltrating T lymphocytes.Journal for immunotherapy of cancer · 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
- Graded diacylglycerol kinases α and ζ activities ensure mucosal-associated invariant T-cell development in mice.European journal of immunology · 2020Article
- Beyond the Cell Surface: Targeting Intracellular Negative Regulators to Enhance T cell Anti-Tumor Activity.International journal of molecular sciences · 2019Review
- DGK α and ζ Activities Control TFrontiers in immunology · 2019Article
- Diacylglycerol kinase α inactivation is an integral component of the costimulatory pathway that amplifies TCR signals.Cancer immunology, immunotherapy : CII · 2018Article
- SNX27 links DGKζ to the control of transcriptional and metabolic programs in T lymphocytes.Scientific reports · 2017Article
- Diacylglycerol Kinase ζ Limits Cytokine-dependent Expansion of CD8EBioMedicine · 2017Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diacylglycerol kinase (DGK)-mediated consumption of the diacylglycerol (DAG) generated in response to antigen recognition is an important mechanism to limit T-cell function. Targeting DGK activity presents new opportunities for therapeutic manipulation of the immune response, but assessment of individual DGK functions is complex. T cells express two DGK isoforms, DGKα and DGKζ, and there are no isoform-specific inhibitors. Here we used short interfering RNA-mediated gene silencing in human T cells and DGKα- and DGKζ-deficient mice to define DGK isoform-specific regulation of key signaling pathways during T-cell activation. Our results identify DGKζ as the predominant brake on basal/tonic conditions as well as on downstream T-cell receptor/co-stimulatory signals. DGKζ silencing triggers basal RasGTP activation and facilitates enhanced membrane stability of protein kinase C alpha as well as increased activity of AGC kinases. Downstream of T-cell receptor/co-stimulation, DGKζ silencing results in enhanced and maintained recruitment of PKC theta to the membrane, as well as phosphoinositide-dependent protein kinase-1 activation and scaffolding functions. Our studies identify a previously unrecognized DGKζ contribution as a negative regulator of the crosstalk between phospholipase C-gamma- and phosphoinositide 3-kinase-regulated pathways. This DGKζ input helps to explain previous observations in DGK-deficient mice and suggests that the development of isoform-specific DGK inhibitors is of great interest for the manipulation of distinct aspects of T-cell responses.
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Registered trials
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