Phosphorylation and Activation of p70 s6k by PDK1
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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mTOR phosphorylates p70S6K at multiple residues, increasing its kinase activity.
“mTOR phosphorylates p70S6 kinase (p70S6K) at several residues, resulting in increased kinase activity (31).”
From Mislocalization of the Cell Polarity Protein Scribble Promotes Mammary Tumorigenesis and Is Associated with Basal Breast Cancer (2014) · cites this paper as [31]
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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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