ArticleCellular signalling2014
RhoA modulates signaling through the mechanistic target of rapamycin complex 1 (mTORC1) in mammalian cells.
Article in Cellular signalling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 68 citations in OpenAlex.
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- Effects of branched-chain amino acids on the muscle-brain metabolic axis: enhancing energy metabolism and neurological functions, and endurance exercise in aging-related conditions.Frontiers in nutrition · 2025Review
- Dystrophin S3059 phosphorylation partially attenuates denervation atrophy in mouse tibialis anterior muscles.Physiological reports · 2024Article
- TRPS1 maintains luminal progenitors in the mammary gland by repressing SRF/MRTF activity.Breast cancer research : BCR · 2024Article
- Vaginal epithelial dysfunction is mediated by the microbiome, metabolome, and mTOR signaling.Cell reports · 2023Article
- Genetics, environmental stress, and amino acid supplementation affect lactational performance via mTOR signaling pathway in bovine mammary epithelial cells.Frontiers in genetics · 2023Review
- Look who's TORking: mTOR-mediated integration of cell status and external signals during limb development and endochondral bone growth.Frontiers in cell and developmental biology · 2023Review
- Matrix stiffness regulates lipid nanoparticle-mRNA delivery in cell-laden hydrogels.Nanomedicine : nanotechnology, biology, and medicine · 2022Article
- Essential Amino Acids and Protein Synthesis: Insights into Maximizing the Muscle and Whole-Body Response to Feeding.Nutrients · 2020Article
- The membrane-associated form of cyclin D1 enhances cellular invasion.Oncogenesis · 2020Article
- Complex interplay between autophagy and oxidative stress in the development of pulmonary disease.Redox biology · 2020Review
- Regulation of mTORC1 by Upstream Stimuli.Genes · 2020Review
- A time course for markers of protein synthesis and degradation with hindlimb unloading and the accompanying anabolic resistance to refeeding.Journal of applied physiology (Bethesda, Md. : 1985) · 2020Article
- Relationship between PI3K/mTOR/RhoA pathway-regulated cytoskeletal rearrangements and phagocytic capacity of macrophages.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2020Article
- Mutations in the sonic hedgehog pathway cause macrocephaly-associated conditions due to crosstalk to the PI3K/AKT/mTOR pathway.American journal of medical genetics. Part A · 2019Article
- Low RhoA expression is associated with adverse outcome in melanoma patients: a clinicopathological analysis.American journal of translational research · 2019Article
- RhoA G17V is sufficient to induce autoimmunity and promotes T-cell lymphomagenesis in mice.Blood · 2018Article
- Simulated Microgravity Reduces Focal Adhesions and Alters Cytoskeleton and Nuclear Positioning Leading to Enhanced Apoptosis via Suppressing FAK/RhoA-Mediated mTORC1/NF-κB and ERK1/2 Pathways.International journal of molecular sciences · 2018Article
- Mechanism and medical implications of mammalian autophagy.Nature reviews. Molecular cell biology · 2018Review
- Simulated microgravity inhibits cell focal adhesions leading to reduced melanoma cell proliferation and metastasis via FAK/RhoA-regulated mTORC1 and AMPK pathways.Scientific reports · 2018Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The mechanistic target of rapamycin (mTOR) in complex 1 (mTORC1) pathway integrates signals generated by hormones and nutrients to control cell growth and metabolism. The activation state of mTORC1 is regulated by a variety of GTPases including Rheb and Rags. Recently, Rho1, the yeast ortholog of RhoA, was shown to interact directly with TORC1 and repress its activation state in yeast. Thus, the purpose of the present study was to test the hypothesis that the RhoA GTPase modulates signaling through mTORC1 in mammalian cells. In support of this hypothesis, exogenous overexpression of either wild type or constitutively active (ca)RhoA repressed mTORC1 signaling as assessed by phosphorylation of p70S6K1 (Thr389), 4E-BP1 (Ser65) and ULK1 (Ser757). Additionally, RhoA·GTP repressed phosphorylation of mTORC1-associated mTOR (Ser2481). The RhoA·GTP mediated repression of mTORC1 signaling occurred independent of insulin or leucine induced stimulation. In contrast to the action of Rho1 in yeast, no evidence was found to support a direct interaction of RhoA·GTP with mTORC1. Instead, expression of caRheb, but not caRags, was able to rescue the RhoA·GTP mediated repression of mTORC1 suggesting RhoA functions upstream of Rheb to repress mTORC1 activity. Consistent with this suggestion, RhoA·GTP repressed phosphorylation of TSC2 (Ser939), PRAS40 (Thr246), Akt (Ser473), and mTORC2-associated mTOR (Ser2481). Overall, the results support a model in which RhoA·GTP represses mTORC1 signaling upstream of Akt and mTORC2.
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Registered trials
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.