ArticleMolecular cell2016
The Lipid Kinase PI5P4Kβ Is an Intracellular GTP Sensor for Metabolism and Tumorigenesis.
Article in Molecular cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed.
- LARS regulates cellular senescence and autophagy in liver cancer cells.Cell death & disease · 2026Article
- PI4K and PIPK families in breast cancer: subtype-specific oncogenic mechanisms and precision therapeutic strategies.Molecular biology reports · 2026Review
- Article
- Orthosteric-allosteric dual inhibitors of PI5P4Kγ with potent antitumor activity in non-small cell lung cancer.Journal of advanced research · 2026Article
- Structural basis for high-affinity inhibitor binding to lipid kinases PIP4K2A and PIP4K2B.Acta crystallographica. Section D, Structural biology · 2026Article
- Article
- IMPDH and GTP Metabolism in Cancer: Mechanisms, Regulation, and Translational Scope.Cancer science · 2025Review
- PI5P4K inhibitors: promising opportunities and challenges.The FEBS journal · 2025Review
- An advanced toolset to manipulate and monitor subcellular phosphatidylinositol 3,5-bisphosphate.The Journal of cell biology · 2025Article
- Phosphoinositide kinases in cancer: from molecular mechanisms to therapeutic opportunities.Nature reviews. Cancer · 2025Review
- Tubulin and GTP Are Crucial Elements for Postsynaptic Density Construction and Aggregation.Journal of neurochemistry · 2025Article
- Deciphering the Population Characteristics of Leiqiong Cattle Using Whole-Genome Sequencing Data.Animals : an open access journal from MDPI · 2025Article
- Review
- PIP4K2B Protein Regulation by NSD1 in HPV-Negative Head and Neck Squamous Cell Carcinoma.Cancers · 2024Article
- Homogeneous luminescent quantitation of cellular guanosine and adenosine triphosphates (GTP and ATP) using QT-LucAnalytical and bioanalytical chemistry · 2023Article
- Multimodal action of KRP203 on phosphoinositide kinases in vitro and in cells.Biochemical and biophysical research communications · 2023Article
- The rational design of ARUK2007145, a dual inhibitor of the α and γ isoforms of the lipid kinase phosphatidylinositol 5-phosphate 4-kinase (PI5P4K).RSC medicinal chemistry · 2023Article
- Functional molecular evolution of a GTP sensing kinase: PI5P4Kβ.The FEBS journal · 2023Article
- Beyond PI3Ks: targeting phosphoinositide kinases in disease.Nature reviews. Drug discovery · 2023Review
- The Identification of Potent, Selective, and Brain Penetrant PI5P4Kγ Inhibitors as In Vivo-Ready Tool Molecules.Journal of medicinal chemistry · 2023Article
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21 authors.
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Abstract
While cellular GTP concentration dramatically changes in response to an organism's cellular status, whether it serves as a metabolic cue for biological signaling remains elusive due to the lack of molecular identification of GTP sensors. Here we report that PI5P4Kβ, a phosphoinositide kinase that regulates PI(5)P levels, detects GTP concentration and converts them into lipid second messenger signaling. Biochemical analyses show that PI5P4Kβ preferentially utilizes GTP, rather than ATP, for PI(5)P phosphorylation, and its activity reflects changes in direct proportion to the physiological GTP concentration. Structural and biological analyses reveal that the GTP-sensing activity of PI5P4Kβ is critical for metabolic adaptation and tumorigenesis. These results demonstrate that PI5P4Kβ is the missing GTP sensor and that GTP concentration functions as a metabolic cue via PI5P4Kβ. The critical role of the GTP-sensing activity of PI5P4Kβ in cancer signifies this lipid kinase as a cancer therapeutic target.
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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.