ArticleThe EMBO journal2011
Dephosphorylation of Carma1 by PP2A negatively regulates T-cell activation.
Article in The EMBO journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 80 citations in OpenAlex.
- PPP2R3C serves as a negative regulator associated with reduced T cell hyperactivation and renal protection in lupus.Clinical and translational medicine · 2026Article
- Decreased expression of circ-CCDC134 mediated by TNF-α in patients with rheumatoid arthritis affects T cell function via targeting protein phosphatase 2A.Arthritis research & therapy · 2026Article
- Phosphatases in tumor cell immune escape: a perspective based on the camouflage, coercion, cytoprotection.Frontiers in cell and developmental biology · 2026Review
- Targeting PP2A in cancer: an underrated option.Journal of experimental & clinical cancer research : CR · 2025Review
- A combination of protein phosphatase 2A inhibition and checkpoint immunotherapy: a perfect storm.Molecular oncology · 2024Review
- Senotherapeutic Peptide 14 Suppresses Th1 and M1 Human T Cell and Monocyte Subsets In Vitro.Cells · 2024Article
- African swine fever virus structural protein p17 inhibits IRF3 activation by recruiting host protein PR65A and inducing apoptotic degradation of STING.Frontiers in microbiology · 2024Article
- Protein Phosphatase 2A: Role in T Cells and Diseases.Journal of immunology research · 2023Review
- LFA-1 cluster formation in T-cells depends on L-plastin phosphorylation regulated by P90Cellular and molecular life sciences : CMLS · 2021Article
- PPP2R2B downregulation is associated with immune evasion and predicts poor clinical outcomes in triple-negative breast cancer.Cancer cell international · 2021Article
- PP2A and Its Inhibitors in Helper T-Cell Differentiation and Autoimmunity.Frontiers in immunology · 2021Review
- Cellular CARD11 Inhibits the Fusogenic Activity of Newcastle Disease Virus via CBM Signalosome-Mediated Furin Reduction in Chicken Fibroblasts.Frontiers in microbiology · 2021Article
- Protein interactome of the Cancerous Inhibitor of protein phosphatase 2A (CIP2A) in Th17 cells.Current research in immunology · 2020Article
- Proteome analysis revealed the essential functions of protein phosphatase PP2A in the induction of Th9 cells.Scientific reports · 2020Article
- Beyond the Cell Surface: Targeting Intracellular Negative Regulators to Enhance T cell Anti-Tumor Activity.International journal of molecular sciences · 2019Review
- Dok3-protein phosphatase 1 interaction attenuates Card9 signaling and neutrophil-dependent antifungal immunity.The Journal of clinical investigation · 2019Article
- CARD-BCL-10-MALT1 signalling in protective and pathological immunity.Nature reviews. Immunology · 2019Review
- Protein Phosphatase 1α and Cofilin Regulate Nuclear Translocation of NF-κB and Promote Expression of the Anti-Inflammatory Cytokine Interleukin-10 by T Cells.Molecular and cellular biology · 2018Article
- Targeting TRAF6 E3 ligase activity with a small-molecule inhibitor combats autoimmunity.The Journal of biological chemistry · 2018Article
- Evolving mechanisms of vascular smooth muscle contraction highlight key targets in vascular disease.Biochemical pharmacology · 2018Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Carma1-Bcl10-Malt1 (CBM) complex bridges T-cell receptor (TCR) signalling to the canonical IκB kinase (IKK)/NF-κB pathway. NF-κB activation is triggered by PKCθ-dependent phosphorylation of Carma1 after TCR/CD28 co-stimulation. PKCθ-phosphorylated Carma1 was suggested to function as a molecular scaffold that recruits preassembled Bcl10-Malt1 complexes to the membrane. We have identified the serine-threonine protein phosphatase PP2A regulatory subunit Aα (PPP2R1A) as a novel interaction partner of Carma1. PPP2R1A is associated with Carma1 in resting as well as activated T cells in the context of the active CBM complex. By siRNA-mediated knockdown and in vitro dephosphorylation, we demonstrate that PP2A removes PKCθ-dependent phosphorylation of Ser645 in Carma1, and show that maintenance of this phosphorylation is correlated with increased T-cell activation. As a result of PP2A inactivation, we find that enhanced Carma1 S645 phosphorylation augments CBM complex formation, NF-κB activation and IL-2 or IFN-γ production after stimulation of Jurkat T cells or murine Th1 cells. Thus, our data define PP2A-mediated dephosphorylation of Carma1 as a critical step to limit T-cell activation and effector cytokine 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.