ArticleProceedings of the National Academy of Sciences of the United States of America2016
In B cells, phosphatidylinositol 5-phosphate 4-kinase-α synthesizes PI(4,5)P2 to impact mTORC2 and Akt signaling.
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 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- PI4K and PIPK families in breast cancer: subtype-specific oncogenic mechanisms and precision therapeutic strategies.Molecular biology reports · 2026Review
- Orthosteric-allosteric dual inhibitors of PI5P4Kγ with potent antitumor activity in non-small cell lung cancer.Journal of advanced research · 2026Article
- Phosphoinositide kinases in cancer: from molecular mechanisms to therapeutic opportunities.Nature reviews. Cancer · 2025Review
- Monoclonal antibody generation by controlled immunoglobulin gene rearrangements.Communications biology · 2025Article
- 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
- Nonlinear dynamics in phosphoinositide metabolism.Current opinion in cell biology · 2024Review
- PI3P-dependent regulation of cell size and autophagy by phosphatidylinositol 5-phosphate 4-kinase.Life science alliance · 2023Article
- Nuclear Phosphoinositides as Key Determinants of Nuclear Functions.Biomolecules · 2023Review
- Beyond PI3Ks: targeting phosphoinositide kinases in disease.Nature reviews. Drug discovery · 2023Review
- Development of potent and selective degraders of PI5P4Kγ.European journal of medicinal chemistry · 2023Article
- Lipid kinases PIP5Ks and PIP4Ks: potential drug targets for breast cancer.Frontiers in oncology · 2023Review
- PIP kinases: A versatile family that demands further therapeutic attention.Advances in biological regulation · 2023Article
- Mechanism of the Regulation of Plasma Cholesterol Levels by PI(4,5)PAdvances in experimental medicine and biology · 2023Article
- The inositol 5-phosphatase INPP5B regulates B cell receptor clustering and signaling.The Journal of cell biology · 2022Article
- Development of Selective Phosphatidylinositol 5-Phosphate 4-Kinase γ Inhibitors with a Non-ATP-competitive, Allosteric Binding Mode.Journal of medicinal chemistry · 2022Article
- Pharmacological inhibition of PI5P4Kα/β disrupts cell energy metabolism and selectively kills p53-null tumor cells.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Targeting the PI5P4K Lipid Kinase Family in Cancer Using Covalent Inhibitors.Cell chemical biology · 2020Article
- Discovery and Structure-Activity Relationship Study of (Journal of medicinal chemistry · 2020Article
- Structure-Activity Relationship Study of Covalent Pan-phosphatidylinositol 5-Phosphate 4-Kinase Inhibitors.ACS medicinal chemistry letters · 2020Article
- Phosphatidylinositol 5 Phosphate 4-Kinase Regulates Plasma-Membrane PIPCell reports · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Phosphatidylinositol 5-phosphate 4-kinases (PI5P4Ks) are enigmatic lipid kinases with physiological functions that are incompletely understood, not the least because genetic deletion and cell transfection have led to contradictory data. Here, we used the genetic tractability of DT40 cells to create cell lines in which endogenous PI5P4Kα was removed, either stably by genetic deletion or transiently (within 1 h) by tagging the endogenous protein genomically with the auxin degron. In both cases, removal impacted Akt phosphorylation, and by leaving one PI5P4Kα allele present but mutating it to be kinase-dead or have PI4P 5-kinase activity, we show that all of the effects on Akt phosphorylation were dependent on the ability of PI5P4Kα to synthesize phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] rather than to remove PI5P. Although stable removal of PI5P4Kα resulted in a pronounced decrease in Akt phosphorylation at Thr308 and Ser473, in part because of reduced plasma membrane PIP3, its acute removal led to an increase in Akt phosphorylation only at Ser473. This process invokes activation primarily of mammalian target of rapamycin complex 2 (mTORC2), which was confirmed by increased phosphorylation of other mTORC2 substrates. These findings establish PI5P4Kα as a kinase that synthesizes a physiologically relevant pool of PI(4,5)P2 and as a regulator of mTORC2, and show a phenomenon similar to the "butterfly effect" described for phosphatidylinositol 3-kinase Iα [Hart JR, et al. (2015) Proc Natl Acad Sci USA 112(4):1131-1136], whereby through apparently the same underlying mechanism, the removal of a protein's activity from a cell can have widely divergent effects depending on the time course of that removal.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.