ArticleScience signaling2016
Binding of the cytoplasmic domain of CD28 to the plasma membrane inhibits Lck recruitment and signaling.
Article in Science signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 59 citations in OpenAlex.
- Membrane-Based Assembly and Interactions in Immune Receptors.Chemical reviews · 2026Review
- PD1-induced Shp2 condensation organizes inhibitory signalosomes through selective substrate partitioning.bioRxiv : the preprint server for biology · 2026Article
- Synthetic mechanoreceptor engineering: From genetic encoding to DNA nanotechnology-based reprogramming.Mechanobiology in medicine · 2025Review
- CD28 signaling complexes are correlated with patient outcomes in anti-CD19 41BB-costimulation CAR T cell therapy.Journal for immunotherapy of cancer · 2025Article
- A CARMIL2 gain-of-function mutation suffices to trigger most CD28 costimulatory functions in vivo.The Journal of experimental medicine · 2025Article
- MARC, a novel modular chimeric antigen receptor, improves T cell-based cancer immunotherapies by preventing early T cell exhaustion and enhancing persistence.Journal for immunotherapy of cancer · 2025Article
- Charge-based immunoreceptor signalling in health and disease.Nature reviews. Immunology · 2025Review
- From TCR fundamental research to innovative chimeric antigen receptor design.Nature reviews. Immunology · 2025Review
- Charged substrate treatment enhances T cell mediated cancer immunotherapy.Nature communications · 2025Article
- CD28 co-stimulation: novel insights and applications in cancer immunotherapy.Nature reviews. Immunology · 2024Review
- CD28 shapes T cell receptor signaling by regulating Lck dynamics and ZAP70 activation.Frontiers in immunology · 2024Article
- Review
- cis-B7:CD28 interactions at invaginated synaptic membranes provide CD28 co-stimulation and promote CD8Immunity · 2023Article
- KIR signaling is regulated by electrostatic interaction of its cytosolic tail with the plasma membrane despite being neutral polyampholyte.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Recent advances in understanding TCR signaling: a synaptic perspective.Faculty reviews · 2023Review
- Emerging CAR T Cell Strategies for the Treatment of AML.Cancers · 2022Review
- Article
- Identification of Biomarkers Related to Regulatory T Cell Infiltration in Oral Squamous Cell Carcinoma Based on Integrated Bioinformatics Analysis.International journal of general medicine · 2022Article
- Determination of the molecular reach of the protein tyrosine phosphatase SHP-1.Biophysical journal · 2021Article
- Structure of the Signal Transduction Domain in Second-Generation CAR Regulates the Input Efficiency of CAR Signals.International journal of molecular sciences · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The T cell costimulatory receptor CD28 is required for the full activation of naïve T cells and for the development and maintenance of Foxp3(+) regulatory T (Treg) cells. We showed that the cytoplasmic domain of CD28 was bound to the plasma membrane in resting cells and that ligand binding to CD28 resulted in its release. Membrane binding by the CD28 cytoplasmic domain required two clusters of basic amino acid residues, which interacted with the negatively charged inner leaflet of the plasma membrane. These same clusters of basic residues also served as interaction sites for Lck, a Src family kinase critical for CD28 function. This signaling complex was further stabilized by the Lck-mediated phosphorylation of CD28 Tyr(207) and the subsequent binding of the Src homology 2 (SH2) domain of Lck to this phosphorylated tyrosine. Mutation of the basic clusters in the CD28 cytoplasmic domain reduced the recruitment to the CD28-Lck complex of protein kinase Cθ (PKCθ), which serves as a key effector kinase in the CD28 signaling pathway. Consequently, mutation of either a basic cluster or Tyr(207) impaired CD28 function in mice as shown by the reduced thymic differentiation of FoxP3(+) Treg cells. On the basis of these results, we propose a previously undescribed model for the initiation of CD28 signaling.
Indexed as
Identifiers
What OpenQuestion holds
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.