ArticleThe Journal of biological chemistry2011
Transforming growth factor-beta-activated kinase 1 regulates natural killer cell-mediated cytotoxicity and cytokine production.
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 20 papers.
What it found
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Targeting TRIM29 As a Negative Regulator of CAR-NK Cell Effector Function to Improve Antitumor Efficacy of these Cells: A Perspective.Current molecular medicine · 2024Review
- Identification of PANoptosis-Based Prognostic Signature for Predicting Efficacy of Immunotherapy and Chemotherapy in Hepatocellular Carcinoma.Genetics research · 2023Article
- Redox regulation of the immune response.Cellular & molecular immunology · 2022Review
- Implications of a 'Third Signal' in NK Cells.Cells · 2021Review
- Tumor-derived NKG2D ligand sMIC reprograms NK cells to an inflammatory phenotype through CBM signalosome activation.Communications biology · 2021Article
- TXNIP Regulates Natural Killer Cell-Mediated Innate Immunity by Inhibiting IFN-γ Production during Bacterial Infection.International journal of molecular sciences · 2020Article
- Molecular mechanisms of FasL-mediated 'reverse-signaling'.Molecular immunology · 2020Review
- Article
- Controlling Cytokine Release Syndrome to Harness the Full Potential of CAR-Based Cellular Therapy.Frontiers in oncology · 2019Review
- Dextran Enhances the Lentiviral Transduction Efficiency of Murine and Human Primary NK Cells.Journal of visualized experiments : JoVE · 2018Article
- Natural Killer Cells: Development, Maturation, and Clinical Utilization.Frontiers in immunology · 2018Review
- Transforming growth factor β activated kinase 1: a potential therapeutic target for rheumatic diseases.Rheumatology (Oxford, England) · 2017Review
- Ceramide inhibits PKCθ by regulating its phosphorylation and translocation to lipid rafts in Jurkat cells.Immunologic research · 2016Article
- TAK1 deficiency in dendritic cells inhibits adaptive immunity in SRBC-immunized C57BL/6 mice.FEBS open bio · 2016Article
- Signaling in Effector Lymphocytes: Insights toward Safer Immunotherapy.Frontiers in immunology · 2016Review
- Signaling by Fyn-ADAP via the Carma1-Bcl-10-MAP3K7 signalosome exclusively regulates inflammatory cytokine production in NK cells.Nature immunology · 2013Article
- ADAPted secretion of cytokines in NK cells.Nature immunology · 2013Article
- A new type of microglia gene targeting shows TAK1 to be pivotal in CNS autoimmune inflammation.Nature neuroscience · 2013Article
- The role of CARMA1 in T cells.Critical reviews in immunology · 2013Review
- IL-22 from conventional NK cells is epithelial regenerative and inflammation protective during influenza infection.Mucosal immunology · 2013Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Carma1, a caspase recruitment domain-containing membrane-associated guanylate kinase, initiates a unique signaling cascade via Bcl10 and Malt1 in NK cells. Carma1 deficiency results in reduced phosphorylation of JNK1/2 and activation of NF-κB that lead to impaired NK cell-mediated cytotoxicity and cytokine production. However, the precise identities of the downstream signaling molecules that link Carma1 to these effector functions were not defined. Here we show that transforming growth factor-β (TGF-β)-activated kinase 1 (TAK1) is abundantly present in NK cells, and activation via NKG2D results in its phosphorylation. Lack of Carma1 considerably reduced TAK1 phosphorylation, demonstrating the dependence of TAK1 on Carma1 in NKG2D-mediated NK cell activations. Pharmacological inhibitor to TAK1 significantly reduced NK-mediated cytotoxicity and its potential to generate IFN-γ, GM-CSF, MIP-1α, MIP-1β, and RANTES. Conditional in vivo knockdown of TAK1 in NK cells from Mx1Cre(+)TAK1(fx/fx) mice resulted in impaired NKG2D-mediated cytotoxicity and cytokine/chemokine production. Inhibition or conditional knockdown of TAK1 severely impaired the NKG2D-mediated phosphorylation of ERK1/2 and JNK1/2 and activation of NF-κB and AP1. Our results show that TAK1 links Carma1 to NK cell-mediated effector functions.
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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.