ArticlePloS one2013
The role of phospholipase D in modulating the MTOR signaling pathway in polycystic kidney disease.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- CAB39 K196 Decrotonylation Drives Psoriasis Pathogenesis by Modulating Keratinocyte Proliferation and Glycolysis.Journal of cellular physiology · 2026Article
- Molecular Mechanisms of Epigenetic Regulation, Inflammation, and Cell Death in ADPKD.Frontiers in molecular biosciences · 2022Review
- Effects of dietary n-3-PUFA supplementation, post-insemination plane of nutrition and pregnancy status on the endometrial transcriptome of beef heifers.Scientific reports · 2020Article
- Development of an miRNA-Array-Based Diagnostic Signature for Periodontitis.Frontiers in genetics · 2020Article
- Phospholipase D2 in prostate cancer: protein expression changes with Gleason score.British journal of cancer · 2019Article
- Therapeutic potential of a phospholipase D1 inhibitory peptide fused with a cell-penetrating peptide as a novel anti-asthmatic drug in a Der f 2-induced airway inflammation model.Experimental & molecular medicine · 2018Article
- Phospholipase D inhibitors reduce human prostate cancer cell proliferation and colony formation.British journal of cancer · 2018Article
- Targeting Phospholipase D4 Attenuates Kidney Fibrosis.Journal of the American Society of Nephrology : JASN · 2017Article
- PLD1 regulates adipogenic differentiation through mTOR - IRS-1 phosphorylation at serine 636/639.Scientific reports · 2016Article
- Unsaturated fatty acids induce non-canonical autophagy.The EMBO journal · 2015Article
- New strategy for in vitro activation of primordial follicles with mTOR and PI3K stimulators.Cell cycle (Georgetown, Tex.) · 2015Article
- Lipoxins: nature's way to resolve inflammation.Journal of inflammation research · 2015Review
- Phospholipase D signaling pathways and phosphatidic acid as therapeutic targets in cancer.Pharmacological reviews · 2014Review
- Genetic mechanisms and signaling pathways in autosomal dominant polycystic kidney disease.The Journal of clinical investigation · 2014Review
- The cytoplasmic tail of FPC antagonizes the full-length protein in the regulation of mTOR pathway.PloS one · 2014Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mammalian target of rapamycin (mTOR) signaling pathway is aberrantly activated in polycystic kidney disease (PKD). Emerging evidence suggests that phospholipase D (PLD) and its product phosphatidic acid (PA) regulate mTOR activity. In this study, we assessed in vitro the regulatory function of PLD and PA on the mTOR signaling pathway in PKD. We found that the basal level of PLD activity was elevated in PKD cells. Targeting PLD by small molecule inhibitors reduced cell proliferation and blocked mTOR signaling, whereas exogenous PA stimulated mTOR signaling and abolished the inhibitory effect of PLD on PKD cell proliferation. We also show that blocking PLD activity enhanced the sensitivity of PKD cells to rapamycin and that combining PLD inhibitors and rapamycin synergistically inhibited PKD cell proliferation. Furthermore, we demonstrate that targeting mTOR did not induce autophagy, whereas targeting PLD induced autophagosome formation. Taken together, our findings suggest that deregulated mTOR pathway activation is mediated partly by increased PLD signaling in PKD cells. Targeting PLD isoforms with pharmacological inhibitors may represent a new therapeutic strategy in PKD.
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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.