The emerging mechanisms of isoform-specific PI3K signalling
Abstract
Phosphoinositide 3-kinases (PI3Ks) function early in intracellular signal transduction pathways and affect many biological functions. A further level of complexity derives from the existence of eight PI3K isoforms, which are divided into class I, class II and class III PI3Ks. PI3K signalling has been implicated in metabolic control, immunity, angiogenesis and cardiovascular homeostasis, and is one of the most frequently deregulated pathways in cancer. PI3K inhibitors have recently entered clinical trials in oncology. A better understanding of how the different PI3K isoforms are regulated and control signalling could uncover their roles in pathology and reveal in which disease contexts their blockade could be most beneficial.
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The three classes of PI3Ks (I, II and III) differ in substrate specificity, and Class I PI3Ks selectively recognise and phosphorylate PI(4,5)P2.
“The three classes (Classes I, II and III) of these enzymes differ in their substrate specificity; the Class I PI3Ks selectively recognises and phosphorylates PI(4,5)P2 (reviewed in [60–63]).”
From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [60]
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- Authors
- Vanhaesebroeck, B., Guillermet-Guibert, J., Graupera, M., & Bilanges, B.
- Affiliations
- Queen Mary University of London (GB)
- Corresponding author
- Vanhaesebroeck, Bart
- Venue
- Nature Reviews Molecular Cell Biology
- Published
- 2010-04-09
- Volume
- 11
- Issue
- 5
- Pages
- 329-341
- ISSN
- 1471-0072 (ISSN-L)
- 1471-0080
- OpenAlex
- W2057370954
- Cited by
- 1,767
- References
- 6
- Citations by year
- 2026: 60 · 2025: 106 · 2024: 99 · 2023: 114 · 2022: 106 · 2021: 134 · 2020: 139 · 2019: 124 · 2018: 117 · 2017: 107 · 2016: 105 · 2015: 116 · 2014: 127 · 2013: 98 · 2012: 116
- FWCI
- 8.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Molecular Cell Biology (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Cancer Research UK
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- phosphatidylinositol 3-kinase, PI3K isoforms, class I PI3K, class II PI3K, class III PI3K, signal transduction, cancer, PI3K inhibitors, metabolic control, immunity, angiogenesis, cardiovascular homeostasis
- MeSH terms
- Animals, Humans, Isoenzymes, Mutation, Neoplasms, Signal Transduction, Phosphatidylinositol 3-Kinases
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