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Cited by 953PI3K/AKT/mTOR signaling in cancerMetabolism, Diabetes, and CancerProtein Kinase Regulation and GTPase Signaling

The DOI matches its Crossref record; 333 of the 338 references it cites were found in a registry or an index.

Phosphoinositide 3-kinase: the key switch mechanism in insulin signalling

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SHEPHERD, Peter R., WITHERS, Dominic J., SIDDLE, Kenneth·1998·Biochemical Journal
DOI 10.1042/bj3330471PMC PMC1219607
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Abstract

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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Metadata

Authors
SHEPHERD, P. R., WITHERS, D. J., & SIDDLE, K.
Affiliations
  • University College London (GB)
  • Joslin Diabetes Center (US)
  • University of Cambridge (GB)
ORCID
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
DOI
10.1042/bj3330471
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
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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