ArticleThe Biochemical journal2013
Evolutionarily conserved structural changes in phosphatidylinositol 5-phosphate 4-kinase (PI5P4K) isoforms are responsible for differences in enzyme activity and localization.
Article in The Biochemical journal, 2013. 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, 71 citations in OpenAlex.
- PIP4K2A depletion suppresses AKT signaling and enhances chemotherapy sensitivity in T-cell lymphoblastic lymphoma cells.Biochemical and biophysical research communications · 2026Article
- 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
- Matrix stiffness induces CaExperimental hematology & oncology · 2026Article
- Structure-Activity Relationship Study of 3-Alkynyl-6-aryl-isothiazolo[4,3-Pharmaceuticals (Basel, Switzerland) · 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
- 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
- Hippo and PI5P4K signaling intersect to control the transcriptional activation of YAP.Science signaling · 2024Article
- 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
- PI3P-dependent regulation of cell size and autophagy by phosphatidylinositol 5-phosphate 4-kinase.Life science alliance · 2023Article
- A novel homeostatic mechanism tunes PI(4,5)P2-dependent signaling at the plasma membrane.Journal of cell science · 2023Article
- Nuclear Phosphoinositides as Key Determinants of Nuclear Functions.Biomolecules · 2023Review
- Identification of ARUK2002821 as an isoform-selective PI5P4Kα inhibitor.RSC medicinal chemistry · 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
- PI5P4Kα supports prostate cancer metabolism and exposes a survival vulnerability during androgen receptor inhibition.Science advances · 2023Article
- 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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2 authors at 1 institution in 1 country.
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Abstract
Mammals have genes coding for three PI5P4Ks (PtdIns5P 4-kinases), and these have different cellular localizations, tissue distributions and lipid kinase activities. We describe in the present paper a detailed molecular exploration of human PI5P4Ks α, β and γ, as well as their fly and worm homologues, to understand how and why these differences came to be. The intrinsic ATPase activities of the three isoforms are very similar, and we show that differences in their G-loop regions can account for much of their wide differences in lipid kinase activity. We have also undertaken an extensive in silico evolutionary study of the PI5P4K family, and show experimentally that the single PI5P4K homologues from Caenorhabditis elegans and Drosophila melanogaster are as widely different in activity as the most divergent mammalian isoforms. Finally we show that the close association of PI5P4Ks α and γ is a true heterodimerization, and not a higher oligomer association of homodimers. We reveal that structural modelling is consistent with this and with the apparently random heterodimerization that we had earlier observed between PI5P4Kα and PI5P4Kβ [Wang, Bond, Letcher, Richardson, Lilley, Irvine and Clarke (2010), Biochem. J. 430, 215-221]. Overall the molecular diversity of mammalian PI5P4Ks explains much of their properties and behaviour, but their physiological functionality remains elusive.
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