ArticleThe Journal of experimental medicine1998
Control of lytic function by mitogen-activated protein kinase/extracellular regulatory kinase 2 (ERK2) in a human natural killer cell line: identification of perforin and granzyme B mobilization by functional ERK2.
Article in The Journal of experimental medicine, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 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
49 citing papers in PubMed, 146 citations in OpenAlex.
- Interleukin-2-stimulated natural killer cells are less susceptible to mycophenolate mofetil than non-activated NK cells: possible consequences for immunotherapy.Cancer immunology, immunotherapy : CII · 2014Trial
- Research progress on the role and dysregulation of NK cells in anti-tuberculosis immunity.Frontiers in immunology · 2026Review
- Natural killer cell-specific chimeric antigen receptor enhances CAR NK cell functions and anti-tumor activity.Theranostics · 2025Article
- NKG2A genetic deletion promotes human primary NK cell anti-tumor responses better than an anti-NKG2A monoclonal antibody.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- CD8Nature reviews. Immunology · 2022Review
- The CD226-ERK1/2-LAMP1 pathway is an important mechanism for Vγ9Vδ2 T cell cytotoxicity against chemotherapy-resistant acute myeloid leukemia blasts and leukemia stem cells.Cancer science · 2021Article
- Detecting cord blood cell type-specific epigenetic associations with gestational diabetes mellitus and early childhood growth.Clinical epigenetics · 2021Article
- Article
- Tumor- and cytokine-primed human natural killer cells exhibit distinct phenotypic and transcriptional signatures.PloS one · 2019Article
- Transcriptome Analysis of Bronchoalveolar Lavage Fluid From Children WithFrontiers in immunology · 2018Article
- IL-21-mediated reversal of NK cell exhaustion facilitates anti-tumour immunity in MHC class I-deficient tumours.Nature communications · 2017Article
- Impaired calcium mobilization in natural killer cells from chronic fatigue syndrome/myalgic encephalomyelitis patients is associated with transient receptor potential melastatin 3 ion channels.Clinical and experimental immunology · 2017Article
- A Two-Phase Expansion Protocol Combining Interleukin (IL)-15 and IL-21 Improves Natural Killer Cell Proliferation and Cytotoxicity against Rhabdomyosarcoma.Frontiers in immunology · 2017Article
- ERK1/2, MEK1/2 and p38 downstream signalling molecules impaired in CD56 dim CD16+ and CD56 bright CD16 dim/- natural killer cells in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients.Journal of translational medicine · 2016Article
- Dysregulation of Protein Kinase Gene Expression in NK Cells from Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Patients.Gene regulation and systems biology · 2016Article
- Therapeutic activity of multiple common γ-chain cytokine inhibition in acute and chronic GVHD.Blood · 2015Article
- Cytokine therapy reverses NK cell anergy in MHC-deficient tumors.The Journal of clinical investigation · 2014Article
- Effects of butyltins on mitogen-activated-protein kinase kinase kinase and Ras activity in human natural killer cells.Journal of applied toxicology : JAT · 2014Article
- The Critical Role of IL-15-PI3K-mTOR Pathway in Natural Killer Cell Effector Functions.Frontiers in immunology · 2014Article
- Suppression of natural killer cells by sorafenib contributes to prometastatic effects in hepatocellular carcinoma.PloS one · 2013Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
The signal pathways that control effector function in human natural killer (NK) cells are little known. In this study, we have identified the critical role of the mitogen-activated protein kinase (MAPK) pathway in NK lysis of tumor cells, and this pathway may involve the mobilization of granule components in NK cells upon interaction with sensitive tumor target cells. Evidence was provided by biological, biochemical, and gene transfection methods. NK cell binding to tumor cells for 5 min was sufficient to maximally activate MAPK/extracellular signal-regulatory kinase 2 (ERK2), demonstrated by its tyrosine phosphorylation and by its ability to function as an efficient kinase for myelin basic protein. MAPK activation was achieved in NK cells only after contact with NK-sensitive but not NK-resistant target cells. In immunocytochemical studies, cytoplasmic perforin and granzyme B were both maximally redirected towards the tumor contact zone within 5 min of NK cell contact with tumor cells. A specific MAPK pathway inhibitor, PD098059, could block not only MAPK activation but also redistribution of perforin/granzyme B in NK cells, which occur upon target ligation. PD098059 also interfered with NK lysis of tumor cells in a 5-h 51Cr-release assay, but had no ability to block NK cell proliferation. Transient transfection studies with wild-type and dominant-negative MAPK/ERK2 genes confirmed the importance of MAPK in NK cell lysis. These results document a pivotal role of MAPK in NK effector function, possibly by its control of movement of lytic granules, and clearly define MAPK involvement in a functional pathway unlinked to cell growth or differentiation.
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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.