The Croonian Lecture 1998. Identification of a protein kinase cascade of major importance in insulin signal transduction
Open accessAbstract
Diabetes affects 3% of the European population and 140 million people worldwide, and is largely a disease of insulin resistance in which the tissues fail to respond to this hormone. This emphasizes the importance of understanding how insulin signals to the cell's interior. We have recently dissected a protein kinase cascade that is triggered by the formation of the insulin ‘second messenger’ phosphatidylinositide (3,4,5) trisphosphate (PtdIns(3,4,5)P 3 ) and which appears to mediate many of the metabolic actions of this hormone. The first enzyme in the cascade is termed 3–phosphoinositide–dependent protein kinase–1 (PDK1), because it only activates protein kinase B (PKB), the next enzyme in the pathway, in the presence of PtdIns(3,4,5)P 3 . PKB then inactivates glycogen synthase kinase–3 (GSK3). PDK1, PKB and GSK3 regulate many physiological events by phosphorylating a variety of intracellular proteins. In addition, PKB plays an important role in mediating protection against apoptosis by survival factors, such as insulin–like growth factor–1.
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Glycogen synthase is the key insulin-regulated enzyme controlling the rate of muscle glycogen synthesis.
“Glycogen synthase is the key insulin-regulated enzyme that controls the rate of muscle glycogen synthesis [148, 150, 200, 212–214].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [214]
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- Authors
- Cohen, P.
- Affiliations
- University of Dundee (GB)
- Corresponding author
- Cohen, Philip
- ORCID
- Cohen, Philip
- Venue
- Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences
- Publisher
- The Royal Society
- Published
- 1999-02-28
- Volume
- 354
- Issue
- 1382
- Pages
- 485-495
- ISSN
- 0962-8436 (ISSN-L)
- 1471-2970
- PMC
- PMC1692513
- OpenAlex
- W1999328200
- Cited by
- 158
- References
- 84
- Citations by year
- 2026: 1 · 2023: 2 · 2022: 3 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 5 · 2017: 1 · 2016: 3 · 2015: 7 · 2014: 2 · 2013: 4 · 2012: 8
- FWCI
- 1.08
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Philosophical Transactions of the Royal Society B Biological Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (submittedVersion)
- 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
- insulin signaling, protein kinase cascades, PDK1, Akt, glycogen synthase kinase-3, phosphatidylinositol 3,4,5-trisphosphate, insulin resistance, diabetes mellitus, apoptosis, insulin-like growth factor I
- MeSH terms
- Amino Acid Sequence, Diabetes Mellitus, Enzyme Inhibitors, Glycogen, Humans, Insulin, Molecular Sequence Data, Phosphorylation, Proteins, Proto-Oncogene Proteins, Receptor, Insulin, Signal Transduction, Apoptosis, Protein Serine-Threonine Kinases, Calcium-Calmodulin-Dependent Protein Kinases, Phosphatidylinositol Phosphates, Glycogen Synthase Kinases, Glycogen Synthase Kinase 3, Proto-Oncogene Proteins c-akt, 3-Phosphoinositide-Dependent Protein Kinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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