ArticleProceedings of the National Academy of Sciences of the United States of America2016
Deletion of the gene Pip4k2c, a novel phosphatidylinositol kinase, results in hyperactivation of the immune system.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 64 citations in OpenAlex.
- Article
- Orthosteric-allosteric dual inhibitors of PI5P4Kγ with potent antitumor activity in non-small cell lung cancer.Journal of advanced research · 2026Article
- Cellular Context Influences Kinase Inhibitor Selectivity.Journal of medicinal chemistry · 2026Article
- Cellular Selectivity Analyses Reveal Distinguishing Profiles for Type II Kinase Inhibitors.bioRxiv : the preprint server for biology · 2025Article
- PI5P4K inhibitors: promising opportunities and challenges.The FEBS journal · 2025Review
- Downregulation of PIP4K2C inhibits the breast cancer cell proliferation, migration and invasion.Translational oncology · 2025Article
- Phosphoinositide kinases in cancer: from molecular mechanisms to therapeutic opportunities.Nature reviews. Cancer · 2025Review
- Evaluating sample normalization methods for MS-based multi-omics and the application to a neurodegenerative mouse model.The Analyst · 2025Article
- LRG1 and SDR16C5 protein expressions differ according to HPV status in oropharyngeal squamous cell carcinoma.Scientific reports · 2024Article
- MTM1-mediated production of phosphatidylinositol 5-phosphate fuels the formation of podosome-like protrusions regulating myoblast fusion.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- PI3P-dependent regulation of cell size and autophagy by phosphatidylinositol 5-phosphate 4-kinase.Life science alliance · 2023Article
- Altered phenotypes due to genetic interaction between the mouse phosphoinositide biosynthesis genes Fig4 and Pip4k2c.G3 (Bethesda, Md.) · 2023Article
- Beyond PI3Ks: targeting phosphoinositide kinases in disease.Nature reviews. Drug discovery · 2023Review
- Targeting the Dark Lipid Kinase PIP4K2C with a Potent and Selective Binder and Degrader.Angewandte Chemie (International ed. in English) · 2023Article
- Development of potent and selective degraders of PI5P4Kγ.European journal of medicinal chemistry · 2023Article
- PI5P4Kα supports prostate cancer metabolism and exposes a survival vulnerability during androgen receptor inhibition.Science advances · 2023Article
- Identification of a chemical probe for lipid kinase phosphatidylinositol-5-phosphate 4-kinase gamma (PI5P4Kγ).Current research in chemical biology · 2023Article
- Targeting phosphoinositide signaling in cancer: relevant techniques to study lipids and novel avenues for therapeutic intervention.Frontiers in cell and developmental biology · 2023Article
- Lipid kinases PIP5Ks and PIP4Ks: potential drug targets for breast cancer.Frontiers in oncology · 2023Review
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Type 2 phosphatidylinositol-5-phosphate 4-kinase (PI5P4K) converts phosphatidylinositol-5-phosphate to phosphatidylinositol-4,5-bisphosphate. Mammals have three enzymes PI5P4Kα, PI5P4Kβ, and PI5P4Kγ, and these enzymes have been implicated in metabolic control, growth control, and a variety of stress responses. Here, we show that mice with germline deletion of type 2 phosphatidylinositol-5-phosphate 4-kinase gamma (Pip4k2c), the gene encoding PI5P4Kγ, appear normal in regard to growth and viability but have increased inflammation and T-cell activation as they age. Immune cell infiltrates increased in Pip4k2c(-/-) mouse tissues. Also, there was an increase in proinflammatory cytokines, including IFNγ, interleukin 12, and interleukin 2 in plasma of Pip4k2c(-/-) mice. Pip4k2c(-/-) mice had an increase in T-helper-cell populations and a decrease in regulatory T-cell populations with increased proliferation of T cells. Interestingly, mammalian target of rapamycin complex 1 (mTORC1) signaling was hyperactivated in several tissues from Pip4k2c(-/-) mice and treating Pip4k2c(-/-) mice with rapamycin reduced the inflammatory phenotype, resulting in a decrease in mTORC1 signaling in tissues and a decrease in proinflammatory cytokines in plasma. These results indicate that PI5P4Kγ plays a role in the regulation of the immune system via mTORC1 signaling.
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