ArticleNature cell biology2019
Phosphorylated Rho-GDP directly activates mTORC2 kinase towards AKT through dimerization with Ras-GTP to regulate cell migration.
Article in Nature cell biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 72 citations in OpenAlex.
- Development of a SIN1 Targeting Inhibitor as a Novel Therapeutic Approach for the Treatment of Malignancies.Molecular cancer therapeutics · 2026Article
- The role of mTOR signaling in regulating the quality of mammalian oocytes.Journal of assisted reproduction and genetics · 2026Review
- PAK1 inhibition synergistically enhances the anti-tumor efficacy of PARP inhibitors in ovarian cancers.Genes & diseases · 2026Article
- Mebendazole Attenuates Cellular Invasion in a 3D Culture Model of Meningioma by Disrupting Rho-GTPase-Mediated Microtubule Function.Oncology research · 2026Article
- Context-dependent inhibitory roles of RhoA in 3D invasive cell migration within the extracellular matrix.Cell reports · 2025Article
- AGPAT2 acts at the crossroads of lipid biosynthesis and DRP1-mediated ER morphogenesis.Nature communications · 2025Article
- Signaling and actin waves at a glance.Journal of cell science · 2025Review
- Rho-GTPases subfamily: cellular defectors orchestrating viral infection.Cellular & molecular biology letters · 2025Review
- Loss of Lkb1 cooperates with BrafMolecular oncology · 2025Article
- Tumor-derived RHOA mutants interact with effectors in the GDP-bound state.Nature communications · 2024Article
- Polyploidy and mTOR signaling: a possible molecular link.Cell communication and signaling : CCS · 2024Review
- Review
- GRHL2-HER3 and E-cadherin mediate EGFR-bypass drug resistance in lung cancer cells.Frontiers in cell and developmental biology · 2024Article
- FilGAP regulates tumor growth in Glioma through the regulation of mTORC1 and mTORC2.Scientific reports · 2023Article
- CRISPR-mediated reversion of oncogenic KRAS mutation results in increased proliferation and reveals independent roles of Ras and mTORC2 in the migration of A549 lung cancer cells.Molecular biology of the cell · 2023Article
- UsingCells · 2023Review
- Expression of mTOR in normal and pathological conditions.Molecular cancer · 2023Review
- Role of FLCN Phosphorylation in Insulin-Mediated mTORC1 Activation and Tumorigenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Mechanosensitive mTORC2 independently coordinates leading and trailing edge polarity programs during neutrophil migration.Molecular biology of the cell · 2023Article
- ELMO1 Deficiency Reduces Neutrophil Chemotaxis in Murine Peritonitis.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
mTORC2 plays critical roles in metabolism, cell survival and actin cytoskeletal dynamics through the phosphorylation of AKT. Despite its importance to biology and medicine, it is unclear how mTORC2-mediated AKT phosphorylation is controlled. Here, we identify an unforeseen principle by which a GDP-bound form of the conserved small G protein Rho GTPase directly activates mTORC2 in AKT phosphorylation in social amoebae (Dictyostelium discoideum) cells. Using biochemical reconstitution with purified proteins, we demonstrate that Rho-GDP promotes AKT phosphorylation by assembling a supercomplex with Ras-GTP and mTORC2. This supercomplex formation is controlled by the chemoattractant-induced phosphorylation of Rho-GDP at S192 by GSK-3. Furthermore, Rho-GDP rescues defects in both mTORC2-mediated AKT phosphorylation and directed cell migration in Rho-null cells in a manner dependent on phosphorylation of S192. Thus, in contrast to the prevailing view that the GDP-bound forms of G proteins are inactive, our study reveals that mTORC2-AKT signalling is activated by Rho-GDP.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.