Cited by 158PI3K/AKT/mTOR signaling in cancerMetabolism, Diabetes, and CancerProtein Kinase Regulation and GTPase Signaling

The Croonian Lecture 1998. Identification of a protein kinase cascade of major importance in insulin signal transduction

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Cohen, Philip·1999·Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences

Abstract

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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Crossref · 10.1098/rstb.1999.0399

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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
Venue
Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences
Published
1999-02-28
Volume
354
Issue
1382
Pages
485-495
ISSN
  • 0962-8436 (ISSN-L)
  • 1471-2970
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
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

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