The 70 kDa S6 Kinase Complexes with and Is Activated by the Rho Family G Proteins Cdc42 and Rac1
Open accessAbstract
The 70 kDa ribosomol S6 kinase (pp70S6k) plays an important role in the progression of cells through G1 phase of the cell cycle. However, little is known of the signaling molecules that mediate its activation. We demonstrate that Rho family G proteins regulate pp70S6k activity in vivo. Activated alleles of Cdc42 and Rac1, but not RhoA, stimulate pp70S6k activity in multiple cell types. Activation requires an intact effector domain and isoprenylation of Cdc42 and Rac1. Coexpression of Dbl, an exchange factor for Cdc42, also activates pp70S6k. Growth factor-induced activation of pp70S6k is abrogated by dominant negative alleles of Cdc42 and Rac1. In addition, Cdc42 and Rac1 form GTP-dependent complex with the catalytically inactive form of pp70S6k in vitro and in vivo, suggesting a mechanism by which these G proteins activate pp70S6k.
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Rac1 appears to activate mTOR and its downstream target p70S6K.
“First, Rac1 appears to activate mTOR and its downstream target p70S6K (70-kDa ribosomal S6 kinase) 57, 58, a kinase essential for switching on translation initiation 48, 49.”
From Autism-like social deficit generated by Dock4 deficiency is rescued by restoration of Rac1 activity and NMDA receptor function. (2021) · cites this paper as [57]
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- Authors
- Chou, M. M., & Blenis, J.
- Affiliations
- Harvard University (US)
- Corresponding author
- Blenis, John
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1996-05
- Volume
- 85
- Issue
- 4
- Pages
- 573-583
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1972317299
- Cited by
- 292
- References
- 64
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 4 · 2022: 4 · 2021: 3 · 2020: 2 · 2019: 4 · 2017: 4 · 2016: 1 · 2015: 5 · 2014: 2 · 2013: 5 · 2012: 5
- FWCI
- 13.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Keywords
- Cdc42, Rac1, RhoA, isoprenylation, effector domain, G1 cell cycle progression, growth factor signaling, kinase activation
- MeSH terms
- Wortmannin, Alleles, Androstadienes, Animals, Antifungal Agents, Bacterial Proteins, Bacterial Toxins, Enzyme Activation, Epidermal Growth Factor, Growth Substances, Guanine Nucleotides, Guanosine Triphosphate, Isomerism, Membrane Proteins, Mutation, Phosphorylation, Plant Proteins, Platelet-Derived Growth Factor, Polyenes, Signal Transduction, Retroviridae Proteins, Oncogenic, Gene Expression, 3T3 Cells, Protein Serine-Threonine Kinases, Protein Structure, Tertiary, Phosphotransferases (Alcohol Group Acceptor), Calcium-Calmodulin-Dependent Protein Kinases, Cell Cycle Proteins, GTP-Binding Proteins, Phosphatidylinositol 3-Kinases, Ribosomal Protein S6 Kinases, Sirolimus, GTP Phosphohydrolases, Guanine Nucleotide Exchange Factors, rhoA GTP-Binding Protein, rac GTP-Binding Proteins, cdc42 GTP-Binding Protein, Saccharomyces cerevisiae, Mitogen-Activated Protein Kinases, Escherichia coli Proteins, JNK Mitogen-Activated Protein Kinases, p38 Mitogen-Activated Protein Kinases, Mice
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