Cited by 835PI3K/AKT/mTOR signaling in cancerProtein Kinase Regulation and GTPase SignalingMetabolism, Diabetes, and Cancer

Phosphorylation and Activation of p70 s6k by PDK1

Pullen, Nicholas, Dennis, Patrick B., Andjelkovic, Mirjana, Dufner, Almut, Kozma, Sara C., Hemmings, Brian A., Thomas, George·1998·Science

Abstract

Activation of the protein p70 s6k by mitogens leads to increased translation of a family of messenger RNAs that encode essential components of the protein synthetic apparatus. Activation of the kinase requires hierarchical phosphorylation at multiple sites, culminating in the phosphorylation of the threonine in position 229 (Thr 229 ), in the catalytic domain. The homologous site in protein kinase B (PKB), Thr 308 , has been shown to be phosphorylated by the phosphoinositide-dependent protein kinase PDK1. A regulatory link between p70 s6k and PKB was demonstrated, as PDK1 was found to selectively phosphorylate p70 s6k at Thr 229 . More importantly, PDK1 activated p70 s6k in vitro and in vivo, whereas the catalytically inactive PDK1 blocked insulin-induced activation of p70 s6k .

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Crossref · 10.1126/science.279.5351.707

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13 of 13 references verified0 citation errors · 0 not checkable

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Authors
Pullen, N., Dennis, P. B., Andjelkovic, M., Dufner, A., Kozma, S. C., Hemmings, B. A., & Thomas, G.
Affiliations
  • Friedrich Miescher Institute, Maulbeerstrasse 66, CH-4058, Basel, Switzerland.
  • Friedrich Miescher Institute (CH)
Corresponding author
  • Dennis, Patrick B.
  • Hemmings, Brian A.
  • Thomas, George
Venue
Science
Published
1998-01-30
Volume
279
Issue
5351
Pages
707-710
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2041926656
Cited by
826
References
13
Citations by year
2026: 3 · 2025: 6 · 2024: 13 · 2023: 11 · 2022: 14 · 2021: 20 · 2020: 12 · 2019: 12 · 2018: 10 · 2017: 13 · 2016: 12 · 2015: 21 · 2014: 22 · 2013: 29 · 2012: 29
FWCI
28.89
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
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
p70S6K, PDK1, protein kinase A, protein kinase activation, protein synthesis regulation, insulin signaling, Akt, catalytic domain
MeSH terms
Wortmannin, Amino Acid Sequence, Androstadienes, Animals, Binding Sites, Catalysis, Cell Line, Enzyme Activation, Insulin, Insulin Antagonists, Molecular Sequence Data, Phosphorylation, Phosphothreonine, Polyenes, Proto-Oncogene Proteins, Recombinant Proteins, Protein Serine-Threonine Kinases, Calcium-Calmodulin-Dependent Protein Kinases, Ribosomal Protein S6 Kinases, Sirolimus, Proto-Oncogene Proteins c-akt, Calcium-Calmodulin-Dependent Protein Kinase Type 4, 3-Phosphoinositide-Dependent Protein Kinases

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