ArticleNature communications2019
Shp-2 is critical for ERK and metabolic engagement downstream of IL-15 receptor in NK cells.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- PTPN22 as a novel therapeutic target: a key intracellular checkpoint for NK cell therapy.Journal for immunotherapy of cancer · 2026Article
- RNA mCell investigation · 2025Article
- Targeting Immune Checkpoint Inhibitors for Non-Small-Cell Lung Cancer: Beyond PD-1/PD-L1 Monoclonal Antibodies.Cancers · 2025Review
- Proteomic signatures of vaccine-induced and breakthrough infection-induced host responses to SARS-CoV-2.Vaccine · 2025Article
- Combining RAS(ON) G12C-selective inhibitor with SHP2 inhibition sensitises lung tumours to immune checkpoint blockade.Nature communications · 2024Article
- Development and Application of Rapamycin-regulated Tyrosine Phosphatases.Journal of visualized experiments : JoVE · 2024Article
- Hippo kinases Mst1 and Mst2 maintain NK cell homeostasis by orchestrating metabolic state and transcriptional activity.Cell death & disease · 2024Article
- Spatial interaction and functional status of CD68Frontiers in immunology · 2024Article
- Tyrosine phosphataseFrontiers in immunology · 2024Review
- SHP2: A Pleiotropic Target at the Interface of Cancer and Its Microenvironment.Cancer discovery · 2023Review
- SHP2 regulates adipose maintenance and adipocyte-pancreatic cancer cell crosstalk via PDHA1.Journal of cell communication and signaling · 2023Article
- Signaling Pathways Leading to mTOR Activation Downstream Cytokine Receptors in Lymphocytes in Health and Disease.International journal of molecular sciences · 2023Review
- Myc controls NK cell development, IL-15-driven expansion, and translational machinery.Life science alliance · 2023Article
- Article
- Recent Advances of RNA mCancer treatment and research · 2023Article
- Concomitant deletion of Ptpn6 and Ptpn11 in T cells fails to improve anticancer responses.EMBO reports · 2022Article
- A novel 2B4 receptor leads to worse pregnancy outcomes by facilitating TNF-α and IFN-γ production in dNK cells during Toxoplasma gondii infection.Parasites & vectors · 2022Article
- Cellular signals converge at the NOX2-SHP-2 axis to induce reductive carboxylation in cancer cells.Cell chemical biology · 2022Article
- IL-1R8 silencing improves the anti-tumor function of freshly isolated human NK cells.Journal for immunotherapy of cancer · 2022Article
- Dynamic variability in SHP-1 abundance determines natural killer cell responsiveness.Science signaling · 2021Article
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 5 countries.
Funding
Abstract
The phosphatase Shp-2 was implicated in NK cell development and functions due to its interaction with NK inhibitory receptors, but its exact role in NK cells is still unclear. Here we show, using mice conditionally deficient for Shp-2 in the NK lineage, that NK cell development and responsiveness are largely unaffected. Instead, we find that Shp-2 serves mainly to enforce NK cell responses to activation by IL-15 and IL-2. Shp-2-deficient NK cells have reduced proliferation and survival when treated with high dose IL-15 or IL-2. Mechanistically, Shp-2 deficiency hampers acute IL-15 stimulation-induced raise in glycolytic and respiration rates, and causes a dramatic defect in ERK activation. Moreover, inhibition of the ERK and mTOR cascades largely phenocopies the defect observed in the absence of Shp-2. Together, our data reveal a critical function of Shp-2 as a molecular nexus bridging acute IL-15 signaling with downstream metabolic burst and NK cell expansion.
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Registered trials
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