ArticleBMC immunology2009
Structure-Function analysis of the CTLA-4 interaction with PP2A.
Article in BMC immunology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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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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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- Whole-Transcriptome Profiling of Murine GL261 Glioma Reveals Signatures Consistent with Distinct Immune Reprogramming Induced by Oncolytic Virotherapy with VV-GMCSF-Lact and Anti-PD-1 Therapy.International journal of molecular sciences · 2026Article
- Costimulation loss enhances IL-2-driven Treg generation by PI3K-STAT3 inhibition in CNS autoimmunity.EMBO molecular medicine · 2026Article
- Post-translational modifications of immune checkpoints: molecular mechanisms, tumor microenvironment remodeling, and therapeutic implications.Journal of biomedical science · 2026Review
- Improving Immune Checkpoint Therapy in the Tumor Microenvironment by Targeting T Cell Metabolism.Endocrine, metabolic & immune disorders drug targets · 2026Review
- Protein Phosphatase 2A Promotes CD8Research (Washington, D.C.) · 2025Article
- Current understanding of CTLA-4: from mechanism to autoimmune diseases.Frontiers in immunology · 2023Review
- Current Understanding of Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) Signaling in T-Cell Biology and Disease Therapy.Molecules and cells · 2022Review
- CTLA-4 Facilitates DNA Damage-Induced Apoptosis by Interacting With PP2A.Frontiers in cell and developmental biology · 2022Article
- Review
- Improving CAR T-Cell Persistence.International journal of molecular sciences · 2021Review
- Metabolic Reprogramming in the Tumor Microenvironment With Immunocytes and Immune Checkpoints.Frontiers in oncology · 2021Review
- Beyond T-Cells: Functional Characterization of CTLA-4 Expression in Immune and Non-Immune Cell Types.Frontiers in immunology · 2020Review
- T Cell Dysfunction in Cancer.Cancer cell · 2018Review
- Toward Small-Molecule Inhibition of Protein-Protein Interactions: General Aspects and Recent Progress in Targeting Costimulatory and Coinhibitory (Immune Checkpoint) Interactions.Current topics in medicinal chemistry · 2018Review
- PP2A as the Main Node of Therapeutic Strategies and Resistance Reversal in Triple-Negative Breast Cancer.Molecules (Basel, Switzerland) · 2017Review
- Checkpoint Inhibitors: Applications for Autoimmunity.Current allergy and asthma reports · 2017Review
- CD28 BlockadeFrontiers in immunology · 2017Article
- Review
- Diverse mechanisms regulate the surface expression of immunotherapeutic target ctla-4.Frontiers in immunology · 2014Review
- Blockade of cytotoxic T-lymphocyte antigen-4 as a new therapeutic approach for advanced melanoma.Expert opinion on pharmacotherapy · 2011Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCTLA-4 functions primarily as an inhibitor of T cell activation. There are several candidate explanations as to how CTLA-4 modulates T cell responses, but the exact mechanism remains undefined. The tail of CTLA-4 does not have any intrinsic enzymatic activity but is able to associate with several signaling molecules including the serine/threonine phosphatase PP2A. PP2A is a heterotrimeric molecule comprised of a regulatory B subunit associated with a core dimer of a scaffolding (A) and a catalytic (C) subunit.
resultsHere, we performed an analysis of the human CTLA-4 interface interacting with PP2A. We show that PP2A interacts with the cytoplasmic tail of CTLA-4 in two different sites, one on the lysine rich motif, and the other on the tyrosine residue located at position 182 (but not the tyrosine 165 of the YVKM motif). Although the interaction between CTLA-4 and PP2A was not required for inhibition of T cell responses, it was important for T cell activation by inverse agonists of CTLA-4. Such an interaction was functionally relevant because the inverse agonists induced IL-2 production in an okadaic acid-dependent manner.
conclusionOur studies demonstrate that PP2A interacts with the cytoplasmic tail of human CTLA-4 through two motifs, the lysine rich motif centered at lysine 155 and the tyrosine residue 182. This interaction and the phosphatase activity of PP2A are important for CTLA-4-mediated T cell activation.
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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.