ArticleNature cell biology2011
Inactivation of Rheb by PRAK-mediated phosphorylation is essential for energy-depletion-induced suppression of mTORC1.
Article in Nature cell biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
88 citing papers in PubMed, 138 citations in OpenAlex.
- FXR1-Directed Alternative Splicing of MK5 Drives Hepatocellular Carcinoma Progression by Activating GSK3β Signaling.Cancer science · 2026Article
- Bioinformatic Analyses of the Ataxin-2 Family Since Algae Emphasize Its Small Isoforms, Large Chimerisms, and the Importance of Human Exon 1B as Target of Therapies to Prevent Neurodegeneration.International journal of molecular sciences · 2026Article
- Exercise-induced irisin ameliorates cognitive impairment following chronic cerebral hypoperfusion by suppressing neuroinflammation and hippocampal neuronal apoptosis.Journal of neuroinflammation · 2025Article
- MK5 Regulates Microglial Activation and Neuroinflammation in Experimental Stroke Models.CNS neuroscience & therapeutics · 2025Article
- Article
- Stress response regulation of mRNA translation: Implications for antioxidant enzyme expression in cancer.Proceedings of the National Academy of Sciences of the United States of America · 2024Review
- Glucose deprivation triggers DCAF1-mediated inactivation of Rheb-mTORC1 and promotes cancer cell survival.Cell death & disease · 2024Article
- Interplay of energy metabolism and autophagy.Autophagy · 2024Review
- LncRNA-HOTAIRM1 promotes aerobic glycolysis and proliferation in osteosarcoma via the miR-664b-3p/Rheb/mTOR pathway.Cancer science · 2023Article
- Polo-like kinase 1 promotes pulmonary hypertension.Respiratory research · 2023Article
- Signaling Pathways Leading to mTOR Activation Downstream Cytokine Receptors in Lymphocytes in Health and Disease.International journal of molecular sciences · 2023Review
- Evolutionary analysis of p38 stress-activated kinases in unicellular relatives of animals suggests an ancestral function in osmotic stress.Open biology · 2023Article
- Enhancing productivity of Chinese hamster ovary (CHO) cells: synergistic strategies combining low-temperature culture and mTORC1 signaling engineering.Frontiers in bioengineering and biotechnology · 2023Article
- The TLK1-MK5 Axis Regulates Motility, Invasion, and Metastasis of Prostate Cancer Cells.Cancers · 2022Article
- TLK1-mediated MK5-S354 phosphorylation drives prostate cancer cell motility and may signify distinct pathologies.Molecular oncology · 2022Article
- Lysosomes at the Crossroads of Cell Metabolism, Cell Cycle, and Stemness.International journal of molecular sciences · 2022Review
- The AMPK pathway in fatty liver disease.Frontiers in physiology · 2022Review
- The Essential Role of PRAK in Preserving Cardiac Function and Insulin Resistance in High-Fat Diet-Induced Diabetes.International journal of molecular sciences · 2021Article
- The essential role of PRAK in tumor metastasis and its therapeutic potential.Nature communications · 2021Article
- The Roles of Post-Translational Modifications on mTOR Signaling.International journal of molecular sciences · 2021Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Cell growth can be suppressed by stressful environments, but the role of stress pathways in this process is largely unknown. Here we show that a cascade of p38β mitogen-activated protein kinase (MAPK) and p38-regulated/activated kinase (PRAK) plays a role in energy-starvation-induced suppression of mammalian target of rapamycin (mTOR), and that energy starvation activates the p38β-PRAK cascade. Depletion of p38β or PRAK diminishes the suppression of mTOR complex 1 (mTORC1) and reduction of cell size induced by energy starvation. We show that p38β-PRAK operates independently of the known mTORC1 inactivation pathways--phosphorylation of tuberous sclerosis protein 2 (TSC2) and Raptor by AMP-activated protein kinase (AMPK)--and surprisingly, that PRAK directly regulates Ras homologue enriched in brain (Rheb), a key component of the mTORC1 pathway, by phosphorylation. Phosphorylation of Rheb at Ser 130 by PRAK impairs the nucleotide-binding ability of Rheb and inhibits Rheb-mediated mTORC1 activation. The direct regulation of Rheb by PRAK integrates a stress pathway with the mTORC1 pathway in response to energy depletion.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.