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Cited by 676PI3K/AKT/mTOR signaling in cancerRNA and protein synthesis mechanismsMetabolism, Diabetes, and Cancer

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Ribosomal S6 Kinase Signaling and the Control of Translation

Dufner, Almut, Thomas, George·1999·Experimental Cell Research
DOI 10.1006/excr.1999.4683
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Abstract

The highly homologous 40S ribosomal protein S6 kinases (S6K1 and S6K2) play a key role in the regulation of cell growth by controlling the biosynthesis of translational components which make up the protein synthetic apparatus, most notably ribosomal proteins. In the case of S6K1, at least eight phosphorylation sites are believed to mediate kinase activation in a hierarchical fashion. Activation is initiated by phosphatidylinositide-3OH kinase (PI3K)-mediated phosphorylation of key residues in the carboxy-terminus of the kinase, allowing phosphorylation of a critical residue residing in the activation loop of the catalytic domain by phosphoinositide-dependent kinase 1 (PDK1). The kinases responsible for phosphorylating the carboxy-terminal sites have yet to be identified. Additionally, S6 kinases are under the control of the PI3K relative, mammalian Target Of Rapamycin (mTOR), which may serve an additional function as a checkpoint for amino acid availability. In this review we set out to discuss the present state of knowledge regarding upstream signaling components which have been implicated in the control of S6K1 activation and the role of the kinase in controlling cell growth through regulating ribosome biogenesis at the translational level.

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Metadata

Authors
Dufner, A., & Thomas, G.
Affiliations
Friedrich Miescher Institute (CH)
Corresponding author
Thomas, George
ORCID
Dufner, Almut
Venue
Experimental Cell Research
Publisher
Elsevier BV
Published
1999-11
Volume
253
Issue
1
Pages
100-109
ISSN
0014-4827 (ISSN-L)
DOI
10.1006/excr.1999.4683
OpenAlex
W1963723155
Cited by
676
References
0
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2026: 3 · 2025: 8 · 2024: 7 · 2023: 8 · 2022: 11 · 2021: 20 · 2020: 9 · 2019: 9 · 2018: 13 · 2017: 22 · 2016: 20 · 2015: 24 · 2014: 21 · 2013: 20 · 2012: 28
FWCI
14.81
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Experimental Cell Research (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 › RNA and protein synthesis mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords
RSK, S6K1, S6K2, translational regulation, PI3K signaling, PDK1, mTOR, kinase activation, activation loop, ribosome biogenesis, cell growth regulation, amino acid availability
MeSH terms
Cell Division, Enzyme Activation, Isoenzymes, Protein Kinase C, Protein Biosynthesis, Signal Transduction, Ribosomal Protein S6 Kinases, Sirolimus, Cell Size

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