ArticleProceedings of the National Academy of Sciences of the United States of America2006
CD28-stimulated ERK2 phosphorylation is required for polarization of the microtubule organizing center and granules in YTS NK cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 122 citations in OpenAlex.
- Methods for Probing NK Cell Surveillance of Antigen Presentation.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Transcriptional signature of rapidly responding NK cells reveals S1P5 and CXCR4 as anti-tumor response disruptors.Scientific reports · 2025Article
- Targeting CD5 chimeric antigen receptor-engineered natural killer cells against T-cell malignancies.Experimental hematology & oncology · 2024Article
- CD28 Costimulation Augments CAR Signaling in NK Cells via the LCK/CD3ζ/ZAP70 Signaling Axis.Cancer discovery · 2024Article
- Multivalent adaptor proteins specifically target NK cells carrying a universal chimeric antigen receptor to ErbB2 (HER2)-expressing cancers.Cancer immunology, immunotherapy : CII · 2023Article
- Challenges and new technologies in adoptive cell therapy.Journal of hematology & oncology · 2023Review
- Eradication of CD48-positive tumors by selectively enhanced YTS cells harnessing the lncRNA NeST.iScience · 2023Article
- Targeting immune checkpoints: how to use natural killer cells for fighting against solid tumors.Cancer communications (London, England) · 2023Review
- Actin Retrograde Flow Regulated by the Wiskott-Aldrich Syndrome Protein Drives the Natural Killer Cell Response.Cancers · 2022Article
- NaCancer research communications · 2022Article
- TM4SF5-mediated liver malignancy involves NK cell exhaustion-like phenotypes.Cellular and molecular life sciences : CMLS · 2021Article
- Characterization of IL-2 Stimulation and TRPM7 Pharmacomodulation in NK Cell Cytotoxicity and Channel Co-Localization with PIPInternational journal of environmental research and public health · 2021Article
- Potential Implications of Mammalian Transient Receptor Potential Melastatin 7 in the Pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Review.International journal of environmental research and public health · 2021Review
- The Role of the Cytoskeleton in Regulating the Natural Killer Cell Immune Response in Health and Disease: From Signaling Dynamics to Function.Frontiers in cell and developmental biology · 2021Review
- Genome-wide analyses and functional profiling of human NK cell lines.Molecular immunology · 2019Article
- Natural Killer Cells and Current Applications of Chimeric Antigen Receptor-Modified NK-92 Cells in Tumor Immunotherapy.International journal of molecular sciences · 2019Review
- The Autoimmune Disorder Susceptibility GeneFrontiers in immunology · 2019Article
- Cord blood NK cells engineered to express IL-15 and a CD19-targeted CAR show long-term persistence and potent antitumor activity.Leukemia · 2018Article
- Ginsenoside F1 Promotes Cytotoxic Activity of NK Cells via Insulin-Like Growth Factor-1-Dependent Mechanism.Frontiers in immunology · 2018Article
- Glucosamine prevents polarization of cytotoxic granules in NK-92 cells by disturbing FOXO1/ERK/paxillin phosphorylation.PloS one · 2018Article
2 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Activation of natural killer (NK) cell cytotoxicity requires adhesion and formation of a conjugate with a susceptible target cell, followed by actin polymerization, and polarization of the microtubule organizing center (MTOC) and cytolytic granules to the NK cell immune synapse. Here, by using the YTS NK cell line as a model, CD28 is shown to be an activating receptor. It signals cytotoxicity in a process dependent on phosphoinositide-3 kinase activation, leading to sustained extracellular signal-regulated kinase 2 (ERK2) phosphorylation. ERK and phospho-ERK localize to microtubule filaments. Neither conjugation with targets nor actin polymerization is affected by blocking ERK2 activation. However, both polarization of the MTOC and cytolytic granules to the synaptic region and NK cell cytotoxicity are strongly reduced by blocking ERK2 activation. A role for the CD28/CD80 interaction in cytotoxicity of human peripheral NK cells also was established. By contrast, lymphocyte function-associated antigen 1 (LFA-1) ligation transduces only a transient ERK2 activation and fails to induce killing in YTS cells. Thus, in YTS cells, a CD28 signal is used to polarize the MTOC and cytolytic granules to the NK cell immune synapse by stimulating sustained ERK2 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.