ArticleMolecular cell2014
Ral and Rheb GTPase activating proteins integrate mTOR and GTPase signaling in aging, autophagy, and tumor cell invasion.
Article in Molecular cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 2 of them syntheses that pooled it.
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Who cites it
81 citing papers in PubMed, 2 syntheses or guidelines pooled it, 132 citations in OpenAlex.
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- Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).Autophagy · 2016Guideline
- Enterococcus faecalis Extracellular Vesicles Deliver the Bacterial GTPase Obg to Hijack mTOR Signalling in Hepatocellular Carcinoma.Journal of extracellular vesicles · 2026Article
- Targeting the Ras-Ral Signaling Axis in Type 2 Diabetes Mellitus: A Dual-Modulation Approach to Correcting Insulin Resistance and β-Cell Dysfunction.Pharmaceuticals (Basel, Switzerland) · 2026Review
- RalB promotes lymph node metastasis in tongue squamous cell carcinoma.Genes & genomics · 2025Article
- Novel De Novo RALA Missense Variants Expand the Genotype Spectrum of Hiatt-Neu-Cooper Neurodevelopmental Syndrome.Molecular genetics & genomic medicine · 2025Article
- Genetic Overlap Between Obstructive Sleep Apnea and Ischemic Stroke: A Large-Scale Genome-Wide Cross-Trait Analysis.Nature and science of sleep · 2025Article
- Salmonella exploits membrane reservoirs for invasion of host cells.Nature communications · 2024Article
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- RAL-1 signaling regulates lipid composition inmicroPublication biology · 2024Article
- Mediating kinase activity in Ras-mutant cancer: potential for an individualised approach?Frontiers in pharmacology · 2024Review
- Study on antihepatocellular carcinoma effect of 6-shogaol and curcumin through network-based pharmacological and cellular assay.Frontiers in pharmacology · 2024Article
- TORC1 regulation of dendrite regrowth after pruning is linked to actin and exocytosis.PLoS genetics · 2023Article
- An isoform-specific function of Cdc42 in regulating mammalian Exo70 during axon formation.Life science alliance · 2023Article
- Functional hierarchy among different Rab27 effectors involved in secretory granule exocytosis.eLife · 2023Article
- UPLC-MS based integrated plasma proteomic and metabolomic profiling of TSC-RAML and its relationship with everolimus treatment.Frontiers in molecular biosciences · 2023Article
- Clustering analysis revealed the autophagy classification and potential autophagy regulators' sensitivity of pancreatic cancer based on multi-omics data.Cancer medicine · 2023Article
- Rare CNVs and Known Genes Linked to Macrocephaly: Review of Genomic Loci and Promising Candidate Genes.Genes · 2022Review
- AMPK signaling and its targeting in cancer progression and treatment.Seminars in cancer biology · 2022Review
- Exocyst inactivation in urothelial cells disrupts autophagy and activates non-canonical NF-κB signaling.Disease models & mechanisms · 2022Article
21 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Diverse environmental cues converge on and are integrated by the mTOR signaling network to control cellular growth and homeostasis. The mammalian Tsc1-Tsc2 GTPase activating protein (GAP) heterodimer is a critical negative regulator of Rheb and mTOR activation. The RalGAPα-RalGAPβ heterodimer shares sequence and structural similarity with Tsc1-Tsc2. Unexpectedly, we observed that C. elegans expresses orthologs for the Rheb and RalA/B GTPases and for RalGAPα/β, but not Tsc1/2. This prompted our investigation to determine whether RalGAPs additionally modulate mTOR signaling. We determined that C. elegans RalGAP loss decreased lifespan, consistent with a Tsc-like function. Additionally, RalGAP suppression in mammalian cells caused RalB-selective activation and Sec5- and exocyst-dependent engagement of mTORC1 and suppression of autophagy. Unexpectedly, we also found that Tsc1-Tsc2 loss activated RalA/B independently of Rheb-mTOR signaling. Finally, RalGAP suppression caused mTORC1-dependent pancreatic tumor cell invasion. Our findings identify an unexpected crosstalk and integration of the Ral and mTOR signaling networks.
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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.