ArticleBlood2008
Colocalization of the IL-12 receptor and FcgammaRIIIa to natural killer cell lipid rafts leads to activation of ERK and enhanced production of interferon-gamma.
Article in Blood, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
51 citing papers in PubMed, 74 citations in OpenAlex.
- A Phase I/II Trial of Cetuximab in Combination with Interleukin-12 Administered to Patients with Unresectable Primary or Recurrent Head and Neck Squamous Cell Carcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Trial
- The membrane distal domain of CD16a allosterically regulates NK cell ADCC.bioRxiv : the preprint server for biology · 2026Article
- TLR2 activation potentiates P-glycoprotein-mediated methotrexate efflux and enhances cytotoxicity of human NK cells against acute lymphoblastic leukemia.Frontiers in immunology · 2026Article
- Cholesterol and sphingomyelin are critical for Fcγ receptor-mediated phagocytosis of Cryptococcus neoformans by macrophages.The Journal of biological chemistry · 2021Article
- Spatial organization of FcγR and TLR2/1 on phagosome membranes differentially regulates their synergistic and inhibitory receptor crosstalk.Scientific reports · 2021Article
- Antibody Conjugation of Fluorescent Nanodiamonds for Targeted Innate Immune Cell Activation.ACS applied nano materials · 2021Article
- Plasma Membrane Integrates Biophysical and Biochemical Regulation to Trigger Immune Receptor Functions.Frontiers in immunology · 2021Review
- Noncatalytic Bruton's tyrosine kinase activates PLCγThe Journal of biological chemistry · 2020Article
- Impact of Plasma Membrane Domains on IgG Fc Receptor Function.Frontiers in immunology · 2020Review
- Unleashing Natural Killer Cells in the Tumor Microenvironment-The Next Generation of Immunotherapy?Frontiers in immunology · 2020Review
- NK Cell-Fc Receptors Advance Tumor Immunotherapy.Journal of clinical medicine · 2019Review
- An IL-15-based superagonist ALT-803 enhances the NK cell response to cetuximab-treated squamous cell carcinoma of the head and neck.Cancer immunology, immunotherapy : CII · 2019Article
- Generation of monocyte-derived tumor-associated macrophages using tumor-conditioned media provides a novel method to study tumor-associated macrophages in vitro.Journal for immunotherapy of cancer · 2019Article
- Dominant role of splenic marginal zone lipid rafts in the classical complement pathway againstCell death discovery · 2019Article
- CD33 (Siglec-3) Inhibitory Function: Role in the NKG2D/DAP10 Activating Pathway.Journal of immunology research · 2019Article
- A peptide inhibitor of antibody-dependent cell-mediated cytotoxicity against EGFR/folate receptor-α double positive cells.MedChemComm · 2018Article
- Nitric Oxide Production by Myeloid-Derived Suppressor Cells Plays a Role in Impairing Fc Receptor-Mediated Natural Killer Cell Function.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Memory-Like NK Cells: Remembering a Previous Activation by Cytokines and NK Cell Receptors.Frontiers in immunology · 2018Review
- MICA-Expressing Monocytes Enhance Natural Killer Cell Fc Receptor-Mediated Antitumor Functions.Cancer immunology research · 2017Article
- Biological mechanisms of immune escape and implications for immunotherapy in head and neck squamous cell carcinoma.European journal of cancer (Oxford, England : 1990) · 2017Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Natural killer (NK) cells express an activating receptor for the Fc portion of IgG (FcgammaRIIIa) that mediates interferon (IFN)-gamma production in response to antibody (Ab)-coated targets. We have previously demonstrated that NK cells activated with interleukin-12 (IL-12) in the presence of immobilized IgG secrete 10-fold or more higher levels of IFN-gamma as compared with stimulation with either agent alone. We examined the intracellular signaling pathways responsible for this synergistic IFN-gamma production. NK cells costimulated via the FcR and the IL-12 receptor (IL-12R) exhibited enhanced levels of activated STAT4 and Syk as compared with NK cells stimulated through either receptor alone. Extracellular signal-regulated kinase (ERK) was also synergistically activated under these conditions. Studies with specific chemical inhibitors revealed that the activation of ERK was dependent on the activation of PI3-K, whose activation was dependent on Syk, and that sequential activation of these molecules was required for NK cell IFN-gamma production in response to FcR and IL-12 stimulation. Retroviral transfection of ERK1 into primary human NK cells substantially increased IFN-gamma production in response to immobilized IgG and IL-12, while transfection of human NK cells with a dominant-negative ERK1 abrogated IFN-gamma production. Confocal microscopy and cellular fractionation experiments revealed that FcgammaRIIIa and the IL-12R colocalized to areas of lipid raft microdomains in response to costimulation with IgG and IL-12. Chemical disruption of lipid rafts inhibited ERK signaling in response to costimulation and significantly inhibited IFN-gamma production. These data suggest that dual recruitment of FcgammaRIIIa and the IL-12R to lipid raft microdomains allows for enhanced activation of downstream signaling events that lead to IFN-gamma production.
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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.