ArticleThe Journal of biological chemistry2011
Decreased diacylglycerol metabolism enhances ERK activation and augments CD8+ T cell functional responses.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
43 citing papers in PubMed, 61 citations in OpenAlex.
- A systems and computational biology perspective on advancing CAR therapy.Seminars in cancer biology · 2023Review
- Discovery of Potent, Dual-Inhibitors of Diacylglycerol Kinases Alpha and Zeta Guided by Phenotypic Optimization.ACS medicinal chemistry letters · 2023Article
- Negative intracellular regulators of T-cell receptor (TCR) signaling as potential antitumor immunotherapy targets.Journal for immunotherapy of cancer · 2023Review
- Overarching roles of diacylglycerol signaling in cancer development and antitumor immunity.Science signaling · 2022Review
- Delivering Glioblastoma a Kick-DGKα Inhibition as a Promising Therapeutic Strategy for GBM.Cancers · 2022Review
- Manipulation of diacylglycerol and ERK-mediated signaling differentially controls CD8Frontiers in immunology · 2022Article
- Review
- DGKζ exerts greater control than DGKα over CD8Oncoimmunology · 2021Article
- Interplay Between SNX27 and DAG Metabolism in the Control of Trafficking and Signaling at the IS.International journal of molecular sciences · 2020Review
- The role of diacylglycerol kinases in allergic airway disease.Current opinion in pharmacology · 2020Review
- Diacylglycerol Kinase Alpha in Radiation-Induced Fibrosis: Potential as a Predictive Marker or Therapeutic Target.Frontiers in oncology · 2020Review
- Diacylglycerol kinase ζ promotes allergic airway inflammation and airway hyperresponsiveness through distinct mechanisms.Science signaling · 2019Article
- Structural basis of inactivation of Ras and Rap1 small GTPases by Ras/Rap1-specific endopeptidase from the sepsis-causing pathogenThe Journal of biological chemistry · 2018Article
- Frontline Science: PECAM-1 (CD31) expression in naïve and memory, but not acutely activated, CD8Journal of leukocyte biology · 2018Article
- Diacylglycerol kinase α inactivation is an integral component of the costimulatory pathway that amplifies TCR signals.Cancer immunology, immunotherapy : CII · 2018Article
- Article
- 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
- DGK-α: A Checkpoint in Cancer-Mediated Immuno-Inhibition and Target for Immunotherapy.Frontiers in cell and developmental biology · 2017Article
- Diacylglycerol Kinase ζ Is a Target To Enhance NK Cell Function.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Modulation of T cell receptor signal transduction in CD8(+) T cells represents a novel strategy toward enhancing the immune response to tumor. Recently, levels of guanine exchange factors, RasGRP and SOS, within T cells have been shown to represent a key determinant in the regulation of the analog to the digital activation threshold of Ras. One important for regulating activation levels of RasGRP is diacylglycerol (DAG), and its levels are influenced by diacylglycerol kinase-ζ (DGKζ), which metabolizes DAG into phosphatidic acid, terminating DAG-mediated Ras signaling. We sought to determine whether DGKζ-deficient CD8(+) T cells demonstrated enhanced in vitro responses in a manner predicted by the current model of Ras activation and to evaluate whether targeting this threshold confers enhanced CD8(+) T cell responsiveness to tumor. We observed that DGKζ-deficient CD8(+) T cells conform to most predictions of the current model of how RasGRP levels influence Ras activation. But our results differ in that the EC(50) value of stimulation is not altered for any T cell receptor stimulus, a finding that suggests a further degree of complexity to how DGKζ deficiency affects signals important for Ras and ERK activation. Additionally, we found that DGKζ-deficient CD8(+) T cells demonstrate enhanced responsiveness in a subcutaneous lymphoma model, implicating the analog to a digital conversion threshold as a novel target for potential therapeutic manipulation.
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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.