ArticleeLife2022
Inhibition of SHP-1 activity by PKC-θ regulates NK cell activation threshold and cytotoxicity.
Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 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
9 citing papers in PubMed, 16 citations in OpenAlex.
- Recent Advances in Research on SHP Family Phosphatases: Signal Regulation Mechanisms and Disease Associations.Cell biochemistry and function · 2026Review
- Genetic manipulation of OGT enhances NK cell-mediated cytotoxicity in tumor immunity.Journal of advanced research · 2026Article
- Discovery of a First-in-Class Covalent Allosteric SHP1 Inhibitor with Immunotherapeutic Activity.Angewandte Chemie (International ed. in English) · 2026Article
- Comprehensive multi-omics analysis reveals the prognostic and immune regulatory characteristics of the PTPN family in osteosarcoma.PloS one · 2025Article
- Prospective Molecular Targets for Natural Killer Cell Immunotherapy against Glioblastoma Multiforme.Cells · 2024Review
- Dysfunctional natural killer cells can be reprogrammed to regain anti-tumor activity.The EMBO journal · 2024Article
- Protein Kinase C at the Crossroad of Mutations, Cancer, Targeted Therapy and Immune Response.Biology · 2023Review
- Actin Retrograde Flow Regulated by the Wiskott-Aldrich Syndrome Protein Drives the Natural Killer Cell Response.Cancers · 2022Article
- Critical roles of PTPN family members regulated by non-coding RNAs in tumorigenesis and immunotherapy.Frontiers in oncology · 2022Review
Corrections and comments
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Authors and funding
12 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Natural killer (NK) cells play a crucial role in immunity, killing virally infected and cancerous cells. The balance of signals initiated upon engagement of activating and inhibitory NK receptors with cognate ligands determines killing or tolerance. Nevertheless, the molecular mechanisms regulating rapid NK cell discrimination between healthy and malignant cells in a heterogeneous tissue environment are incompletely understood. The SHP-1 tyrosine phosphatase is the central negative NK cell regulator that dephosphorylates key activating signaling proteins. Though the mechanism by which SHP-1 mediates NK cell inhibition has been partially elucidated, the pathways by which SHP-1 is itself regulated remain unclear. Here, we show that phosphorylation of SHP-1 in NK cells on the S591 residue by PKC-θ promotes the inhibited SHP-1 'folded' state. Silencing PKC-θ maintains SHP-1 in the active conformation, reduces NK cell activation and cytotoxicity, and promotes tumor progression in vivo. This study reveals a molecular pathway that sustains the NK cell activation threshold through suppression of SHP-1 activity.
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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.