ArticleCell death and differentiation2019
Stage-specific requirement of kinase PDK1 for NK cells development and activation.
Article in Cell death and differentiation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Hematopoietic cell-specific knockout Hspa9 impairs natural killer cell function and alters the Akt/mTOR axis in mice.Experimental and therapeutic medicine · 2026Article
- A Microbiota- and IL-15-Dependent Innate-Like B Cell Progenitor Expressing E4BP4.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Melatonin enhances NK cell function in aged mice by increasing T-bet expression via the JAK3-STAT5 signaling pathway.Immunity & ageing : I & A · 2024Article
- A single-cell sequence analysis of mouse subcutaneous white adipose tissue reveals dynamic changes during weaning.Communications biology · 2024Article
- Hippo kinases Mst1 and Mst2 maintain NK cell homeostasis by orchestrating metabolic state and transcriptional activity.Cell death & disease · 2024Article
- Yeast β-glucan modulates macrophages and improves antitumor NK-cell responses in cancer.Clinical and experimental immunology · 2023Article
- Chemokine (C-X-C motif) ligand 1 maintains the immune surveillance function of natural killer cells via the PDK2/mTOR signaling pathway.Cell biology and toxicology · 2023Article
- Transcription factor TOX maintains the expression of Mst1 in controlling the early mouse NK cell development.Theranostics · 2023Article
- A cuproptosis-related genes signature associated with prognosis and immune cell infiltration in osteosarcoma.Frontiers in oncology · 2022Article
- Astragaloside regulates lncRNA LOC100912373 and the miR‑17‑5p/PDK1 axis to inhibit the proliferation of fibroblast‑like synoviocytes in rats with rheumatoid arthritis.International journal of molecular medicine · 2021Article
- The kinase PDK1 regulates regulatory T cell survival via controlling redox homeostasis.Theranostics · 2021Article
- Transcription Factors Associated With IL-15 Cytokine Signaling During NK Cell Development.Frontiers in immunology · 2021Review
- Chronic shift-lag promotes NK cell ageing and impairs immunosurveillance in mice by decreasing the expression of CD122.Journal of cellular and molecular medicine · 2020Article
- Myeloid deletion of phosphoinositide-dependent kinase-1 enhances NK cell-mediated antitumor immunity by mediating macrophage polarization.Oncoimmunology · 2020Article
- Full Activation of Kinase Protein Kinase B by Phosphoinositide-Dependent Protein Kinase-1 and Mammalian Target of Rapamycin Complex 2 Is Required for Early Natural Killer Cell Development and Survival.Frontiers in immunology · 2020Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phosphoinositide-dependent kinase-1 (PDK1) is an important enzyme for immune cell development by connecting PI3K to downstream mTOR signaling. It is needed to investigate how PDK1 spatiotemporally orchestrates NK cells development and whether this kinase is required for NK cells effector function. In this study, we used three genetic models to delete pdk1 at respective developmental stages, including hematopoietic stem cells (Vav1-Cre used), NK cell progenitor (NKp, CD122-Cre used) and terminal NK cells (Ncr1-Cre used). We found that CD122-Cre mediated deletion of pdk1 caused a severe loss of NK cells to an extent comparable to that of deletion by Vav1-Cre, and further revealed that PDK1 was necessary for NK cells master transcription factor E4BP4 expression at the NKp stage. Moreover, Ncr1-Cre-mediated inactivation of pdk1 delayed NK cells terminal differentiation. These PDK1-deficient NK cells secreted decreased amounts of the cytokine IFN-γ, likely due to impaired downstream mTOR activation. They also exhibited reduced degranulation in response to tumor cells. Mechanistically, PDK1 was critical for the formation of NK-target conjugates and lytic synapses. Therefore, we clarify the stage-specific roles of the metabolic regulator PDK1 in NK cells biology.
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