Cited by 834PI3K/AKT/mTOR signaling in cancerProtein Kinase Regulation and GTPase SignalingMetabolism, Diabetes, and Cancer

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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

DOI 10.1126/science.279.5351.707

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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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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
ORCID: Dennis, Patrick B.
Dufner, Almut
Thomas, George
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1998-01-30
Volume: 279
Issue: 5351
Pages: 707-710
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.279.5351.707
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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Phosphorylation and Activation of p70 s6k by PDK1

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