ArticleThe Journal of biological chemistry2015
Reciprocal regulation of AMP-activated protein kinase and phospholipase D.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
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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
48 citing papers in PubMed, 86 citations in OpenAlex.
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- Autophagy and autophagy signaling in Epilepsy: possible role of autophagy activator.Molecular medicine (Cambridge, Mass.) · 2023Review
- Activity-based directed evolution of a membrane editor in mammalian cells.Nature chemistry · 2023Article
- Genomic signature of MTOR could be an immunogenicity marker in human colorectal cancer.BMC cancer · 2022Article
- Article
- Empagliflozin activates Sestrin2-mediated AMPK/mTOR pathway and ameliorates lipid accumulation in obesity-related nonalcoholic fatty liver disease.Frontiers in pharmacology · 2022Article
- AMPK-mTOR Signaling and Cellular Adaptations in Hypoxia.International journal of molecular sciences · 2021Review
- New Insight into the Effects of Metformin on Diabetic Retinopathy, Aging and Cancer: Nonapoptotic Cell Death, Immunosuppression, and Effects beyond the AMPK Pathway.International journal of molecular sciences · 2021Review
- Feedback, Crosstalk and Competition: Ingredients for Emergent Non-Linear Behaviour in the PI3K/mTOR Signalling Network.International journal of molecular sciences · 2021Review
- Metformin induces Ferroptosis by inhibiting UFMylation of SLC7A11 in breast cancer.Journal of experimental & clinical cancer research : CR · 2021Article
- ERK activation via A1542/3 limonoids attenuates erythroleukemia through transcriptional stimulation of cholesterol biosynthesis genes.BMC cancer · 2021Article
- Apigenin role as cell-signaling pathways modulator: implications in cancer prevention and treatment.Cancer cell international · 2021Review
- The Metabolic Landscape of RAS-Driven Cancers from biology to therapy.Nature cancer · 2021Review
- KRASInternational journal of molecular sciences · 2021Article
- The Role of mTOR Signaling as a Therapeutic Target in Cancer.International journal of molecular sciences · 2021Review
- Raptor and rictor expression in patients with human papillomavirus-related oropharyngeal squamous cell carcinoma.BMC cancer · 2021Article
- Macrophage Autophagy and Silicosis: Current Perspective and Latest Insights.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
AMP-activated protein kinase (AMPK), a critical sensor of energy sufficiency, acts as central metabolic switch in cell metabolism. Once activated by low energy status, AMPK phosphorylates key regulatory substrates and turns off anabolic biosynthetic pathways. In contrast, the mammalian/mechanistic target of rapamycin (mTOR) is active when there are sufficient nutrients for anabolic reactions. A critical factor regulating mTOR is phosphatidic acid (PA), a central metabolite of membrane lipid biosynthesis and the product of the phospholipase D (PLD)-catalyzed hydrolysis of phosphatidylcholine. PLD is a downstream target of the GTPase Rheb, which is turned off in response to AMPK via the tuberous sclerosis complex. Although many studies have linked AMPK with mTOR, very little is known about the connection between AMPK and PLD. In this report, we provide evidence for reciprocal regulation of PLD by AMPK and regulation of AMPK by PLD and PA. Suppression of AMPK activity led to an increase in PLD activity, and conversely, activation of AMPK suppressed PLD activity. Suppression of PLD activity resulted in elevated AMPK activity. Exogenously supplied PA abolished the inhibitory effects of elevated AMPK activity on mTOR signaling. In contrast, exogenously supplied PA could not overcome the effect AMPK activation if either mTOR or Raptor was suppressed, indicating that the inhibitory effects of PLD and PA on AMPK activity are mediated by mTOR. These data suggest a reciprocal feedback mechanism involving AMPK and the PLD/mTOR signaling node in cancer cells with therapeutic implications.
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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.