ArticleFrontiers in immunology2012
Regulation of the PKCθ-NF-κB Axis in T Lymphocytes by the Tumor Necrosis Factor Receptor Family Member OX40.
Article in Frontiers in immunology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- The OX40-OX40L Co-Stimulatory Pathway as a Shared Driver of Immune Persistence in Skin and Airway Inflammation.Clinical reviews in allergy & immunology · 2026Review
- IL-33-primed human mast cells drive IL-9 production by CD4Frontiers in immunology · 2024Article
- Mitochondrial reactive oxygen is critical for IL-12/IL-18-induced IFN-γ production by CD4Cell death & disease · 2022Article
- T cell receptor (TCR) signaling in health and disease.Signal transduction and targeted therapy · 2021Review
- Influence of antigen density and immunosuppressive factors on tumor-targeted costimulation with antibody-fusion proteins and bispecific antibody-mediated T cell response.Cancer immunology, immunotherapy : CII · 2020Article
- Recent insights of T cell receptor-mediated signaling pathways for T cell activation and development.Experimental & molecular medicine · 2020Review
- Ways and waves of MALT1 paracaspase activation.Cellular & molecular immunology · 2018Article
- TNF-α regulates the proteolytic degradation of ST6Gal-1 and endothelial cell-cell junctions through upregulating expression of BACE1.Scientific reports · 2017Article
- Nuclear PKC-θ facilitates rapid transcriptional responses in human memory CD4+ T cells through p65 and H2B phosphorylation.Journal of cell science · 2016Article
- PKC-Theta in Regulatory and Effector T-cell Functions.Frontiers in immunology · 2015Review
- Roles for TNF-receptor associated factor 3 (TRAF3) in lymphocyte functions.Cytokine & growth factor reviews · 2014Review
- Regulation of immune system cell functions by protein kinase C.Frontiers in immunology · 2013Article
- Protein kinase C signaling and cell cycle regulation.Frontiers in immunology · 2012Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
Abstract
Antigen primed T lymphocytes need to expand and persist to promote adaptive immunity. The growth and survival signals that control this are in large part provided by the NF-κB pathway in activated or effector/memory T cells. Although several membrane receptors impact NF-κB activation, signaling from OX40 (CD134, TNFRSF4), a member of the tumor necrosis factor receptor (TNFR) superfamily, has proven to be important for T cell immunity and a strong contributor to NF-κB activity. PKCθ directs the T cell receptor (TCR) and CD28-dependent assembly of a CBM complex (CARMA1, BCL10, and MALT1) for efficient activation of NF-κB, raising the question of whether other membrane bound receptors that activate NF-κB also require this PKCθ-CBM axis to control TCR-independent T cell activity. We discuss here our recent data demonstrating that after ligation by OX40L (CD252, TNFSF4) expressed on antigen-presenting cells, OX40 translocates into detergent-insoluble membrane lipid microdomains (DIM or lipid rafts) in T cells irrespective of TCR signals, and assembles into a signaling complex containing PKCθ, together with TRAF2, RIP1, the CBM complex, and the IKKα/β/Γ complex. PKCθ is required for optimal NF-κB activation mediated by OX40 and thus works as an essential component of this OX40 signalosome. We also discuss the likelihood that other TNFR superfamily molecules might complex with PKCθ in T cells, and whether PKC isoforms may be critical to the function of TNFR molecules in general.
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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.