ArticleThe Journal of experimental medicine2014
EAT-2, a SAP-like adaptor, controls NK cell activation through phospholipase Cγ, Ca++, and Erk, leading to granule polarization.
Article in The Journal of experimental medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 92 citations in OpenAlex.
- NKG2D upregulation sensitizes tumors to combined anti-PD1 and anti-VEGF therapy and prevents hearing loss.Nature communications · 2026Article
- Human lncRNAs NEAT1 and MALAT1 regulate the tumor microenvironment in lung cancer PDX models in athymic nude mice.Scientific reports · 2025Article
- Over-activation and dysfunction of platelet-NK cell aggregates in HIV-infected individuals.Journal of translational medicine · 2025Article
- SLAMF receptors: key regulators of tumor progression and emerging targets for cancer immunotherapy.Molecular cancer · 2025Review
- Article
- Imaging of biphasic signalosomes constructed by checkpoint receptor 2B4 in conventional and chimeric antigen receptor-T cells.iScience · 2025Article
- X-linked lymphoproliferative disease type 1: a clinical and genetic update.Frontiers in immunology · 2025Review
- 2B4/CD244 Signaling in Immune Regulation and Its Role in Infection, Cancer, and Immune Tolerance.ImmunoTargets and therapy · 2025Review
- "Find Me" and "Eat Me" signals: tools to drive phagocytic processes for modulating antitumor immunity.Cancer communications (London, England) · 2024Review
- Elotuzumab Enhances CD16-Independent NK Cell-Mediated Cytotoxicity against Myeloma Cells by Upregulating Several NK Cell-Enhancing Genes.Journal of immunology research · 2024Article
- Therapeutic Targets of Monoclonal Antibodies Used in the Treatment of Cancer: Current and Emerging.Biomedicines · 2023Review
- Single cell transcriptome sequencing of stimulated and frozen human peripheral blood mononuclear cells.Scientific data · 2023Article
- SLAM-family receptors come of age as a potential molecular target in cancer immunotherapy.Frontiers in immunology · 2023Review
- The efficacy of combination treatment with elotuzumab and lenalidomide is dependent on crosstalk between natural killer cells, monocytes and myeloma cells.Haematologica · 2023Article
- Macrophage-mediated anti-tumor immunity against high-risk neuroblastoma.Genes and immunity · 2022Article
- Single-cell profiling of human dura and meningioma reveals cellular meningeal landscape and insights into meningioma immune response.Genome medicine · 2022Article
- Adenoviral delivery of an immunomodulatory protein to the tumor microenvironment controls tumor growth.Molecular therapy oncolytics · 2022Article
- A NK Cell Odyssey: From Bench to Therapeutics Against Hematological Malignancies.Frontiers in immunology · 2022Review
- Selective elimination of immunosuppressive T cells in patients with multiple myeloma.Leukemia · 2021Article
- Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
Ewing's sarcoma-associated transcript 2 (EAT-2) is an Src homology 2 domain-containing intracellular adaptor related to signaling lymphocytic activation molecule (SLAM)-associated protein (SAP), the X-linked lymphoproliferative gene product. Both EAT-2 and SAP are expressed in natural killer (NK) cells, and their combined expression is essential for NK cells to kill abnormal hematopoietic cells. SAP mediates this function by coupling SLAM family receptors to the protein tyrosine kinase Fyn and the exchange factor Vav, thereby promoting conjugate formation between NK cells and target cells. We used a variety of genetic, biochemical, and imaging approaches to define the molecular and cellular mechanisms by which EAT-2 controls NK cell activation. We found that EAT-2 mediates its effects in NK cells by linking SLAM family receptors to phospholipase Cγ, calcium fluxes, and Erk kinase. These signals are triggered by one or two tyrosines located in the carboxyl-terminal tail of EAT-2 but not found in SAP. Unlike SAP, EAT-2 does not enhance conjugate formation. Rather, it accelerates polarization and exocytosis of cytotoxic granules toward hematopoietic target cells. Hence, EAT-2 promotes NK cell activation by molecular and cellular mechanisms distinct from those of SAP. These findings explain the cooperative and essential function of these two adaptors in NK cell activation.
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