Synthesis and Function of 3-Phosphorylated Inositol Lipids
Abstract
▪ Abstract The 3-phosphorylated inositol lipids fulfill roles as second messengers by interacting with the lipid binding domains of a variety of cellular proteins. Such interactions can affect the subcellular localization and aggregation of target proteins, and through allosteric effects, their activity. Generation of 3-phosphoinositides has been documented to influence diverse cellular pathways and hence alter a spectrum of fundamental cellular activities. This review is focused on the 3-phosphoinositide lipids, the synthesis of which is acutely triggered by extracellular stimuli, the enzymes responsible for their synthesis and metabolism, and their cell biological roles. Much knowledge has recently been gained through structural insights into the lipid kinases, their interaction with inhibitors, and the way their 3-phosphoinositide products interact with protein targets. This field is now moving toward a genetic dissection of 3-phosphoinositide action in a variety of model organisms. Such approaches will reveal the true role of the 3-phosphoinositides at the organismal level in health and disease.
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IPMK generates only PI(3,4,5)P3 as its product, unlike class I PI3K which generates multiple products.
“Specifically, IPMK generates only PI (3,4,5) P3 as its product [26], highlighting its unique enzymatic specificity in lipid kinase activity.”
From From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease (2025) · cites this paper as [36]
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From Obscurity to Prominence: IPMK’s Expanding Role in Cellular Signaling, Physiology, and Disease
Mishra, S. H., Chatterjee, S., Viera-Preval, L., & Guha, P. (2025) · Biomolecules · doi:10.3390/biom15091266 · Cited by 1 · see citing works
“Interestingly, in contrast to class I phosphoinositide 3-kinase (PI3K), traditionally considered the primary cellular lipid kinase, generating multiple products such as PI (3,4,5) P3, PI (3,4) P2, and PI (3) P from lipid extracts [26,36], IPMK displays remarkable selectivity.”
- Authors
- Vanhaesebroeck, B., Leevers, S. J., Ahmadi, K., Timms, J., Katso, R., Driscoll, P. C., Woscholski, R., Parker, P. J., & Waterfield, M. D.
- Affiliations
- Ludwig Cancer Research (GB)
- Ludwig Institute for Cancer Research, Riding House Street, London W1W 7BS;
- Venue
- Annual Review of Biochemistry
- Publisher
- Annual Reviews
- Published
- 2001-06
- Volume
- 70
- Issue
- 1
- Pages
- 535-602
- ISSN
- 0066-4154 (ISSN-L)
- 1545-4509
- OpenAlex
- W2164139183
- Cited by
- 1,535
- References
- 9
- Citations by year
- 2026: 10 · 2025: 16 · 2024: 16 · 2023: 19 · 2022: 27 · 2021: 15 · 2020: 29 · 2019: 31 · 2018: 36 · 2017: 42 · 2016: 42 · 2015: 48 · 2014: 57 · 2013: 49 · 2012: 75
- FWCI
- 7.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- lipid kinase, phosphoinositide metabolism, second messengers, protein-lipid interactions, allosteric regulation, phosphoinositide signaling
- MeSH terms
- Wortmannin, Phosphoinositide-3 Kinase Inhibitors, Actins, Androstadienes, Animals, Binding Sites, Blood Proteins, Cell Division, Chromones, Cytoskeleton, Enzyme Inhibitors, Humans, Morpholines, Phosphatidylinositols, Phosphoric Monoester Hydrolases, Phosphoproteins, Apoptosis, Sequence Homology, Amino Acid, Phosphatidylinositol 3-Kinases, 1-Phosphatidylinositol 4-Kinase, Catalytic Domain, Tumor Suppressor Proteins, PTEN Phosphohydrolase
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