ArticleScience signaling2021
Dynamic variability in SHP-1 abundance determines natural killer cell responsiveness.
Article in Science signaling, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Recent Advances in Research on SHP Family Phosphatases: Signal Regulation Mechanisms and Disease Associations.Cell biochemistry and function · 2026Review
- ITPKB is a conserved regulator of natural killer cell desensitization/education that constrains antitumor immunity.bioRxiv : the preprint server for biology · 2026Article
- Discovery of a First-in-Class Covalent Allosteric SHP1 Inhibitor with Immunotherapeutic Activity.Angewandte Chemie (International ed. in English) · 2026Article
- Phosphatases in tumor cell immune escape: a perspective based on the camouflage, coercion, cytoprotection.Frontiers in cell and developmental biology · 2026Review
- Article
- SYK negatively regulates ITAM-mediated human NK cell signaling and CD19-CAR NK cell efficacy.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- NK cells in HPV-related tumorigenesis: mechanisms and clinical applications.Frontiers in cellular and infection microbiology · 2025Review
- Expression of a single inhibitory member of the Ly49 receptor family is sufficient to license NK cells for effector functions.bioRxiv : the preprint server for biology · 2024Article
- Comprehensive snapshots of natural killer cells functions, signaling, molecular mechanisms and clinical utilization.Signal transduction and targeted therapy · 2024Review
- Genetic complexity of killer-cell immunoglobulin-like receptor genes in human pangenome assemblies.Genome research · 2024Article
- Spleen Tyrosine Kinase (SYK) negatively regulates ITAM-mediated human NK cell signaling and CD19-CAR NK cell efficacy.bioRxiv : the preprint server for biology · 2024Article
- Egr2 to the rescue: nanoparticles revitalize natural killer cells in the fight against cancer.The EMBO journal · 2024Article
- Dysfunctional natural killer cells can be reprogrammed to regain anti-tumor activity.The EMBO journal · 2024Article
- Liebig's law of the minimum in the TGF-β/SMAD pathway.PLoS computational biology · 2024Article
- Kir6.1, a component of an ATP-sensitive potassium channel, regulates natural killer cell development.Frontiers in immunology · 2024Article
- Single-cell profiling aligns CD56Frontiers in immunology · 2024Article
- Allelic variation of KIR and HLA tunes the cytolytic payload and determines functional hierarchy of NK cell repertoires.Blood advances · 2023Article
- Human natural killer cells: Form, function, and development.The Journal of allergy and clinical immunology · 2023Review
- Killer instincts: natural killer cells as multifactorial cancer immunotherapy.Frontiers in immunology · 2023Review
- Altered-Self MHC Class I Sensing via Functionally Disparate Paired NK Cell Receptors Counters Murine Cytomegalovirus gp34-Mediated Immune Evasion.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
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Authors and funding
9 authors.
Funding
Abstract
Interactions between human leukocyte antigen (HLA) molecules on target cells and the inhibitory killer cell immunoglobulin-like receptors (KIRs) and heterodimeric inhibitory receptor CD94-NKG2A on human natural killer (NK) cells shape and program various response capacities. A functionally orthologous system exists in mice, consisting of major histocompatibility complex (MHC) molecules on target cells and the inhibitory Ly49 and CD94-NKG2A receptors on NK cells. Here, we found that the abundance of Src homology 2 domain–containing phosphatase-1 (SHP-1) in NK cells was established by interactions between MHCs and NK cell inhibitory receptors, although phenotypically identical NK cell populations still showed substantial variability in endogenous SHP-1 abundance and NK cell response potential. Human and mouse NK cell populations with high responsiveness had low SHP-1 abundance, and a reduction in SHP-1 abundance in NK cells enhanced their responsiveness. Computational modeling of NK cell activation by membrane-proximal signaling events identified SHP-1 as a negative amplitude regulator, which was validated by single-cell analysis of human NK cell responsiveness. The amount of mRNA and protein varied among responsive NK cells despite their similar chromatin accessibility to that of unresponsive cells, suggesting dynamic regulation of SHP-1 abundance. Low intracellular SHP-1 abundance was a biomarker of responsive NK cells. Together, these data suggest that enhancing NK cell function through the acute loss of SHP-1 abundance or activity may enhance the tumoricidal capacity of NK cells.
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