Synergy in activating class I PI3Ks
Abstract
The class I phosphoinositide 3-kinases (PI3Ks) are lipid kinases that transduce a host of cellular signals and regulate a broad range of essential functions including growth, proliferation, and migration. As such, PI3Ks have pivotal roles in diseases such as cancer, diabetes, primary immune disorders, and inflammation. These enzymes are activated downstream of numerous activating stimuli including receptor tyrosine kinases, G protein-coupled receptors (GPCRs), and the Ras superfamily of small G proteins. A major challenge is to decipher how each PI3K isoform is able to successfully synergize these inputs into their intended signaling function. This article highlights recent progress in characterizing the molecular mechanisms of PI3K isoform-specific activation pathways, as well as novel roles for PI3Ks in human diseases, specifically cancer and immune diseases.
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Synergistic activation of specific Class I PI3K isoforms through different signalling inputs is an important aspect of their regulation.
“Notably, synergistic activation of specific Class I PI3K isoforms through different signalling inputs is an important aspect of their regulation [64].”
From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [64]
Cites
RAS Interaction with PI3K: More Than Just Another Effector Pathway
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Self-citationStructural Basis for Activation and Inhibition of Class I Phosphoinositide 3-Kinases
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GPCR activation of Ras and PI3Kγ in neutrophils depends on PLCβ2/β3 and the RasGEF RasGRP4
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The PI3K Pathway in Human Disease
Fruman, D. A., Chiu, H., Hopkins, B. D., Bagrodia, S., Cantley, L. C., & Abraham, R. T. (2017) · Cell · doi:10.1016/j.cell.2017.07.029 · Cited by 2,749 · see citing works
The PI3K/AKT Pathway in Obesity and Type 2 Diabetes
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“RTKs recruit class I PI3Ks to the plasma membrane, which relieves the inactivation function of p85 and p110 to activate the protein [12, 13].”
BackgroundStructural Basis for Regulation of Phosphoinositide Kinases and Their Involvement in Human Disease
Burke, J. E. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.08.005 · Cited by 276 · see citing works
Self-citationPhosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane
Katan, M., & Cockcroft, S. (2020) · Essays in Biochemistry · doi:10.1042/ebc20200041 · Cited by 176 · see citing works
- Authors
- Burke, J. E., & Williams, R. L.
- Affiliations
- University of Victoria (CA)
- MRC Laboratory of Molecular Biology (GB)
- Corresponding author
- Burke, John E.
- ORCID
- Burke, John E.
- Venue
- Trends in Biochemical Sciences
- Publisher
- Elsevier BV
- Published
- 2015-02
- Volume
- 40
- Issue
- 2
- Pages
- 88-100
- ISSN
- 0968-0004 (ISSN-L)
- OpenAlex
- W2063569450
- Cited by
- 216
- References
- 8
- Citations by year
- 2026: 7 · 2025: 24 · 2024: 13 · 2023: 30 · 2022: 24 · 2021: 20 · 2020: 18 · 2019: 21 · 2018: 22 · 2017: 20 · 2016: 9 · 2015: 8
- FWCI
- 1.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Biochemical Sciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- British Heart Foundation (PG/11/109/29247)
- 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 › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- class I PI3K, PI3K isoforms, receptor tyrosine kinase, G protein-coupled receptors, signal transduction, cancer, immune disorders
- MeSH terms
- Cell Movement, Humans, Immune System Diseases, Neoplasms, Phosphatidylinositols, Signal Transduction, Phosphatidylinositol 3-Kinases, Protein Isoforms, Receptors, G-Protein-Coupled, Cell Proliferation
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