ArticleThe Journal of experimental medicine1997
Functional role for Syk tyrosine kinase in natural killer cell-mediated natural cytotoxicity.
Article in The Journal of experimental medicine, 1997. 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
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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
41 citing papers in PubMed, 145 citations in OpenAlex.
- CD28 signaling domain boosts persistence andiScience · 2025Article
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- Evidence and therapeutic implications of biomechanically regulated immunosurveillance in cancer and other diseases.Nature nanotechnology · 2024Review
- NK Cells: Not Just Followers But Also Initiators of Chronic Vascular Rejection.Transplant international : official journal of the European Society for Organ Transplantation · 2024Review
- Natural killer cells: a future star for immunotherapy of head and neck squamous cell carcinoma.Frontiers in immunology · 2024Review
- Spatial requirements for ITAM signaling in an intracellular natural killer cell model membrane.Biochimica et biophysica acta. General subjects · 2022Article
- Clinical development of natural killer cells expressing chimeric antigen receptors.Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis · 2021Review
- Engineering Anti-Tumor Monoclonal Antibodies and Fc Receptors to Enhance ADCC by Human NK Cells.Cancers · 2021Review
- Natural Killer Cells: Tumor Surveillance and Signaling.Cancers · 2020Review
- ZAP-70 Shapes the Immune Microenvironment in B Cell Malignancies.Frontiers in oncology · 2020Review
- Research Progress on NK Cell Receptors and Their Signaling Pathways.Mediators of inflammation · 2020Review
- Spleen Tyrosine Kinase as a Target Therapy for Pseudomonas aeruginosa Infection.Journal of innate immunity · 2018Review
- Differential Requirements for Src-Family Kinases in SYK or ZAP70-Mediated SLP-76 Phosphorylation in Lymphocytes.Frontiers in immunology · 2017Article
- Article
- Article
- Syk negatively regulates TLR4-mediated IFNβ and IL-10 production and promotes inflammatory responses in dendritic cells.Biochimica et biophysica acta · 2016Article
- BTLA marks a less-differentiated tumor-infiltrating lymphocyte subset in melanoma with enhanced survival properties.Oncoimmunology · 2015Article
- Complexity and Diversity of the NKR-P1:Clr (Klrb1:Clec2) Recognition Systems.Frontiers in immunology · 2014Review
- Natural killer cells in patients with severe chronic fatigue syndrome.Auto- immunity highlights · 2013Article
- The role of the cytoskeleton at the immunological synapse.Immunological reviews · 2013Review
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 1 institution in 1 country.
Funding
Abstract
Natural killer (NK) cells are named based on their natural cytotoxic activity against a variety of target cells. However, the mechanisms by which sensitive targets activate killing have been difficult to study due to the lack of a prototypic NK cell triggering receptor. Pharmacologic evidence has implicated protein tyrosine kinases (PTKs) in natural killing; however, Lck-deficient, Fyn-deficient, and ZAP-70-deficient mice do not exhibit defects in natural killing despite demonstrable defects in T cell function. This discrepancy implies the involvement of other tyrosine kinases. Here, using combined biochemical, pharmacologic, and genetic approaches, we demonstrate a central role for the PTK Syk in natural cytotoxicity. Biochemical analyses indicate that Syk is tyrosine phosphorylated after stimulation with a panel of NK-sensitive target cells. Pharmacologic exposure to piceatannol, a known Syk family kinase inhibitor, inhibits natural cytotoxicity. In addition, gene transfer of dominant-negative forms of Syk to NK cells inhibits natural cytotoxicity. Furthermore, sensitive targets that are rendered NK-resistant by major histocompatibility complex (MHC) class I transfection no longer activate Syk. These data suggest that Syk activation is an early and requisite signaling event in the development of natural cytotoxicity directed against a variety of cellular targets.
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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.