ArticleScience signaling2014
Protein kinase D2 is a digital amplifier of T cell receptor-stimulated diacylglycerol signaling in naïve CD8⁺ T cells.
Article in Science signaling, 2014. 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, 38 citations in OpenAlex.
- Murine T-cell receptor OT-I exhibits imperfect discrimination between foreign and self-antigens.The EMBO journal · 2026Article
- Stereoselective Degradation of Diacylglycerol Kinases Potentiate T cell Activation and Tumor Cell Cytotoxicity.bioRxiv : the preprint server for biology · 2025Article
- Discovery of BMS-986408, a First-In-Class Dual DGKα and DGKζ Inhibitor that Unleashes PD-1 Checkpoint and CAR T-cell Immunotherapies.Cancer immunology research · 2025Article
- Time required for commitment to T cell proliferation depends on TCR affinity and cytokine response.EMBO reports · 2023Article
- Addressing the role of PKD3 in the T cell compartment with knockout mice.Cell communication and signaling : CCS · 2022Article
- T cell-intrinsic protein kinase D3 is dispensable for the cells' activation.Frontiers in immunology · 2022Article
- Staggered starts in the race to T cell activation.Trends in immunology · 2021Review
- Signaling through polymerization and degradation: Analysis and simulations of T cell activation mediated by Bcl10.PLoS computational biology · 2021Article
- Perfect adaptation of CD8Science signaling · 2021Article
- Extracellular signal-regulated kinase (ERK) pathway control of CD8+ T cell differentiation.The Biochemical journal · 2021Article
- Stepwise Tfh cell differentiation revisited: new advances and long-standing questions.Faculty reviews · 2021Article
- Human CD8Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Mucosal Vaccination with UV-InactivatedVaccines · 2020Article
- Article
- Mutual inhibition between Prkd2 and Bcl6 controls T follicular helper cell differentiation.Science immunology · 2020Article
- CTL-Derived Exosomes Enhance the Activation of CTLs Stimulated by Low-Affinity Peptides.Frontiers in immunology · 2019Article
- T cell cytolytic capacity is independent of initial stimulation strength.Nature immunology · 2018Article
- Cheating the Hunger Games; Mechanisms Controlling Clonal Diversity of CD8 Effector and Memory Populations.Frontiers in immunology · 2018Review
- Predominant contribution of DGKζ over DGKα in the control of PKC/PDK-1-regulated functions in T cells.Immunology and cell biology · 2017Article
- Lighting Up T Lymphocyte Signaling with Quantitative Phosphoproteomics.Frontiers in immunology · 2017Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Protein kinase D2 (PKD2) is a serine and threonine kinase that is activated in T cells by diacylglycerol and protein kinase C in response to stimulation of the T cell receptor (TCR) by antigen. We quantified the activation of PKD2 at the single-cell level and found that this kinase acts as a sensitive digital amplifier of TCR engagement, enabling CD8(+) T cells to match the production of inflammatory cytokines to the quality and quantity of TCR ligands. There was a digital response pattern of PKD2 activation in response to TCR engagement, such that increasing the concentration and potency of TCR ligands increased the number of cells that exhibited activated PKD2. However, for each cell that responded to TCR stimulation, the entire cellular pool of PKD2 (~400,000 molecules) was activated. Moreover, PKD2 acted as an amplification checkpoint for antigen-stimulated digital cytokine responses and translated the differential strength of TCR signaling to determine the number of naïve CD8(+) T cells that became effector cells. Together, these results provide insights into PKD family kinases and how they act digitally to amplify signaling networks controlled by the TCR.
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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.