ArticleMolecular cell2015
Rapid mitogenic regulation of the mTORC1 inhibitor, DEPTOR, by phosphatidic acid.
Article in Molecular cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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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
60 citing papers in PubMed, 95 citations in OpenAlex.
- Synthetic Lipid Biology.Chemical reviews · 2025Review
- Identification of functional circRNAs regulating ovarian follicle development in goats.BMC genomics · 2024Article
- Comprehensive Review on Bimolecular Fluorescence Complementation and Its Application in Deciphering Protein-Protein Interactions in Cell Signaling Pathways.Biomolecules · 2024Review
- The mTORC2 signaling network: targets and cross-talks.The Biochemical journal · 2024Review
- Identification of the specific molecular and functional signatures of pre-beta-HDL: relevance to cardiovascular disease.Basic research in cardiology · 2023Article
- Activity-based directed evolution of a membrane editor in mammalian cells.Nature chemistry · 2023Article
- The Arf family GTPases: Regulation of vesicle biogenesis and beyond.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Review
- Regulation of mTOR by phosphatidic acid.Trends in endocrinology and metabolism: TEM · 2023Review
- Imaging and Editing the Phospholipidome.Accounts of chemical research · 2022Review
- Article
- Mechanistic Target of Rapamycin Complex 1: From a Nutrient Sensor to a Key Regulator of Metabolism and Health.Advances in nutrition (Bethesda, Md.) · 2022Article
- Upregulated phospholipase D2 expression and activity is related to the metastatic properties of melanoma.Oncology letters · 2022Article
- Chronic Exposure to Palmitic Acid Down-Regulates AKT in Beta-Cells through Activation of mTOR.The American journal of pathology · 2022Article
- Fat of the Gut: Epithelial Phospholipids in Inflammatory Bowel Diseases.International journal of molecular sciences · 2021Review
- Regulation of human mTOR complexes by DEPTOR.eLife · 2021Article
- Bipartite binding and partial inhibition links DEPTOR and mTOR in a mutually antagonistic embrace.eLife · 2021Article
- Optical Control of Phosphatidic Acid Signaling.ACS central science · 2021Article
- CD4mBio · 2020Article
- The first DEP domain of the RhoGEF P-Rex1 autoinhibits activity and contributes to membrane binding.The Journal of biological chemistry · 2020Article
- Amino acid-dependent control of mTORC1 signaling: a variety of regulatory modes.Journal of biomedical science · 2020Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
The mammalian target of rapamycin complex 1 (mTORC1) is regulated, in part, by the endogenous inhibitor DEPTOR. However, the mechanism of DEPTOR regulation with regard to rapid mTORC1 activation remains unknown. We report that DEPTOR is rapidly and temporarily dissociated from mTORC1 upon mitogenic stimulation, suggesting a mechanism underlying acute mTORC1 activation. This mitogen-stimulated DEPTOR dissociation is blocked by inhibition or depletion of the mTORC1 regulator, phospholipase D (PLD), and recapitulated with the addition of the PLD product phosphatidic acid (PA). Our mass spectrometry analysis has independently identified DEPTOR as an mTOR binding partner dissociated by PA. Interestingly, only PA species with unsaturated fatty acid chains, such as those produced by PLD, are capable of displacing DEPTOR and activating mTORC1, with high affinity for the FRB domain of mTOR. Our findings reveal a mechanism of mTOR regulation and provide a molecular explanation for the exquisite specificity of PA function.
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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.