ArticleThe Journal of biological chemistry2011
Phosphatidic acid activates mammalian target of rapamycin complex 1 (mTORC1) kinase by displacing FK506 binding protein 38 (FKBP38) and exerting an allosteric effect.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
What it found
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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.
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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.
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Who cites it
73 citing papers in PubMed, 127 citations in OpenAlex.
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- Plant Exosome-like Nanovesicles and Their Role in the Innovative Delivery of RNA Therapeutics.Biomedicines · 2023Review
- The skeletal muscle fiber periphery: A nexus of mTOR-related anabolism.Sports medicine and health science · 2023Review
- Critical role of the mTOR pathway in poultry skeletal muscle physiology and meat quality: an opinion paper.Frontiers in physiology · 2023Article
- Regulation of Airway Smooth Muscle Cell Proliferation by Diacylglycerol Kinase: Relevance to Airway Remodeling in Asthma.International journal of molecular sciences · 2022Article
- Mechanistic Target of Rapamycin Complex 1: From a Nutrient Sensor to a Key Regulator of Metabolism and Health.Advances in nutrition (Bethesda, Md.) · 2022Article
- Targeting mTOR in the Context of Diet and Whole-body Metabolism.Endocrinology · 2022Review
- 24-Norursodeoxycholic acid reshapes immunometabolism in CD8Journal of hepatology · 2021Article
- Fat of the Gut: Epithelial Phospholipids in Inflammatory Bowel Diseases.International journal of molecular sciences · 2021Review
- BNIP3L/Nix-induced mitochondrial fission, mitophagy, and impaired myocyte glucose uptake are abrogated by PRKA/PKA phosphorylation.Autophagy · 2021Article
- Molecular Regulation of Skeletal Muscle Growth and Organelle Biosynthesis: Practical Recommendations for Exercise Training.International journal of molecular sciences · 2021Review
- Phosphatidic Acid Stimulates Myoblast Proliferation through Interaction with LPA1 and LPA2 Receptors.International journal of molecular sciences · 2021Article
- Research progress and perspective in metabolism and metabolomics of psoriasis.Chinese medical journal · 2020Article
- Regulation of Signaling and Metabolism by Lipin-mediated Phosphatidic Acid Phosphohydrolase Activity.Biomolecules · 2020Review
- Beyond Lipid Signaling: Pleiotropic Effects of Diacylglycerol Kinases in Cellular Signaling.International journal of molecular sciences · 2020Review
- Amino acid-dependent control of mTORC1 signaling: a variety of regulatory modes.Journal of biomedical science · 2020Review
13 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
5 authors at 2 institutions in 1 country.
Funding
Abstract
Phosphatidic acid (PA) is a critical mediator of mitogenic activation of mammalian target of rapamycin complex 1 (mTORC1) signaling, a master regulator of mammalian cell growth and proliferation. The mechanism by which PA activates mTORC1 signaling has remained unknown. Here, we report that PA selectively stimulates mTORC1 but not mTORC2 kinase activity in cells and in vitro. Furthermore, we show that PA competes with the mTORC1 inhibitor, FK506 binding protein 38 (FKBP38), for mTOR binding at a site encompassing the rapamycin-FKBP12 binding domain. This leads to PA antagonizing FKBP38 inhibition of mTORC1 kinase activity in vitro and rescuing mTORC1 signaling from FKBP38 in cells. Phospholipase D 1, a PA-generating enzyme that is an established upstream regulator of mTORC1, is found to negatively affect mTOR-FKBP38 interaction, confirming the role of endogenous PA in this regulation. Interestingly, removal of FKBP38 alone is insufficient to activate mTORC1 kinase and signaling, which require PA even when the FKBP38 level is drastically reduced by RNAi. In conclusion, we propose a dual mechanism for PA activation of mTORC1: PA displaces FKBP38 from mTOR and allosterically stimulates the catalytic activity of mTORC1.
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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 Socratic graph.