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Phosphoinositide 3-kinase: the key switch mechanism in insulin signalling
Open accessAbstract
Insulin plays a key role in regulating a wide range of cellular processes. However, until recently little was known about the signalling pathways that are involved in linking the insulin receptor with downstream responses. It is now apparent that the activation of class 1a phosphoinositide 3-kinase (PI 3-kinase) is necessary and in some cases sufficient to elicit many of insulin's effects on glucose and lipid metabolism. The lipid products of PI 3-kinase act as both membrane anchors and allosteric regulators, serving to localize and activate downstream enzymes and their protein substrates. One of the major ways these lipid products of PI 3-kinase act in insulin signalling is by binding to pleckstrin homology (PH) domains of phosphoinositide-dependent protein kinase (PDK) and protein kinase B (PKB) and in the process regulating the phosphorylation of PKB by PDK. Using mechanisms such as this, PI 3-kinase is able to act as a molecular switch to regulate the activity of serine/threonine-specific kinase cascades important in mediating insulin's effects on endpoint responses.
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“PI 3-kinase is activated when the dimer binds to IRS-1 [9].”
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“PI 3-kinase is a heterodimer composed of a regulatory subunit (p85α) and a catalytic sub-unit (p110)”
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Synthesis and Function of 3-Phosphorylated Inositol Lipids
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Glucose Transporters and Insulin Action — Implications for Insulin Resistance and Diabetes Mellitus
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Metadata
- Authors
- SHEPHERD, P. R., WITHERS, D. J., & SIDDLE, K.
- Affiliations
- University College London (GB)
- Joslin Diabetes Center (US)
- University of Cambridge (GB)
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 1998-08-01
- Volume
- 333
- Issue
- 3
- Pages
- 471-490
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- PMC
- PMC1219607
- OpenAlex
- W1841050729
- Cited by
- 953
- References
- 338
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 7 · 2023: 13 · 2022: 15 · 2021: 7 · 2020: 22 · 2019: 19 · 2018: 13 · 2017: 16 · 2016: 18 · 2015: 29 · 2014: 21 · 2013: 15 · 2012: 31
- FWCI
- 6.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biochemical Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Medical Research Council
- 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, insulin signaling, insulin receptor, phosphoinositide 3-phosphate, pleckstrin homology domain, Akt, allosteric regulation, lipid second messengers, glucose metabolism, lipid metabolism
- MeSH terms
- Animals, Humans, Insulin, Signal Transduction, Phosphatidylinositol 3-Kinases
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