ArticleImmunity2010
Synergistic signals for natural cytotoxicity are required to overcome inhibition by c-Cbl ubiquitin ligase.
Article in Immunity, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 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.
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.
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Who cites it
78 citing papers in PubMed.
- Article
- Nanoscale restructuring of the immune synapse with an engager enhances NK cell function.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Histocompatibility in Botryllus schlosseri and the origins of adaptive immunity.Immunogenetics · 2025Review
- A chimeric antigen receptor tailored to integrate complementary activation signals potentiates the antitumor activity of NK cells.Journal of experimental & clinical cancer research : CR · 2025Article
- Targeting Triple NK Cell Suppression Mechanisms: A Comprehensive Review of Biomarkers in Pancreatic Cancer Therapy.International journal of molecular sciences · 2025Review
- Comprehensive snapshots of natural killer cells functions, signaling, molecular mechanisms and clinical utilization.Signal transduction and targeted therapy · 2024Review
- HPK1 Dysregulation-Associated NK Cell Dysfunction and Defective Expansion Promotes Metastatic Melanoma Progression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The Power of Three: Nanomaterials for Natural Killer (NK) Cell Immunoengineering Maximize Their Potency if They Exploit Multireceptor Stimulation.Advanced healthcare materials · 2024Article
- NK cell-based tumor immunotherapy.Bioactive materials · 2024Review
- Inhibition of SHP-1 activity by PKC-θ regulates NK cell activation threshold and cytotoxicity.eLife · 2022Article
- Poliovirus receptor (PVR)-like protein cosignaling network: new opportunities for cancer immunotherapy.Journal of experimental & clinical cancer research : CR · 2021Review
- Licensing Natural Killers for Antiviral Immunity.Pathogens (Basel, Switzerland) · 2021Review
- Cbl-b Is Upregulated and Plays a Negative Role in Activated Human NK Cells.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Targeting ubiquitin signaling for cancer immunotherapy.Signal transduction and targeted therapy · 2021Review
- NKG2D Engagement Alone Is Sufficient to Activate Cytokine-Induced Killer Cells While 2B4 Only Provides Limited Coactivation.Frontiers in immunology · 2021Article
- Myosin 1g and 1f: A Prospective Analysis in NK Cell Functions.Frontiers in immunology · 2021Review
- Filamin A Is Required for NK Cell Cytotoxicity at the Expense of Cytokine ProductionFrontiers in immunology · 2021Article
- 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
- Arrested development: suppression of NK cell function in the tumor microenvironment.Clinical & translational immunology · 2021Article
- An optimal control approach for enhancing natural killer cells' secretion of cytolytic molecules.APL bioengineering · 2020Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
Abstract
Natural killer (NK) cell cytotoxicity toward target cells depends on synergistic coactivation by NK cell receptors such as NKG2D and 2B4. How synergy occurs is not known. Synergistic phosphorylation of phospholipase PLC-gamma2, Ca(2+) mobilization, and degranulation triggered by NKG2D and 2B4 coengagement were blocked by Vav1 siRNA knockdown, but enhanced by knockdown of c-Cbl. c-Cbl inhibited Vav1-dependent signals, given that c-Cbl knockdown did not rescue the Vav1 defect. Moreover, c-Cbl knockdown and Vav1 overexpression each circumvented the necessity for synergy because NKG2D or 2B4 alone became sufficient for activation. Thus, synergy requires not strict complementation but, rather, strong Vav1 signals to overcome inhibition by c-Cbl. Inhibition of NK cell cytotoxicity by CD94-NKG2A binding to HLA-E on target cells was dominant over synergistic activation, even after c-Cbl knockdown. Therefore, NK cell activation by synergizing receptors is regulated at the level of Vav1 by a hierarchy of inhibitory mechanisms.
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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.