ArticleMolecular and cellular biology2014
Temporal production of the signaling lipid phosphatidic acid by phospholipase D2 determines the output of extracellular signal-regulated kinase signaling in cancer cells.
Article in Molecular and cellular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 124 citations in OpenAlex.
- Endogenous tracking reveals paralog-specific targets for phosphatidic acid generation during phospholipase C signaling in living cells.The Journal of biological chemistry · 2026Article
- Membrane editing with proximity labeling reveals regulators of lipid homeostasis.Nature chemical biology · 2026Article
- Visualizing suborganellar lipid distribution using correlative light and electron microscopy.Nature cell biology · 2026Article
- Article
- Subcellular Cartography of the Phosphoinositide Multiverse.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2026Review
- AGPAT2 acts at the crossroads of lipid biosynthesis and DRP1-mediated ER morphogenesis.Nature communications · 2025Article
- Oleate activates PLD2 lipase and GEF activity by modulating membrane microdomain dynamics via S-acylation.Journal of lipid research · 2025Article
- PILS-Nir1 is a sensitive phosphatidic acid biosensor that reveals mechanisms of lipid production.The Journal of cell biology · 2025Article
- PILS-Nir1 is a novel phosphatidic acid biosensor that reveals mechanisms of lipid production.bioRxiv : the preprint server for biology · 2025Article
- Emerging Approaches for Studying Lipid Dynamics, Metabolism, and Interactions in Cells.Annual review of biochemistry · 2025Review
- Article
- Optogenetic Strategies for Optimizing the Performance of Phospholipids Biosensors.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Calcium influx rapidly establishes distinct spatial recruitments of Annexins to cell wounds.Genetics · 2024Article
- Probing and imaging phospholipid dynamics in live cells.Life metabolism · 2024Review
- Role of phosphatidic acid lipids on plasma membrane association of the Ebola virus matrix protein VP40.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2024Article
- Ultralow Background Membrane Editors for Spatiotemporal Control of Phosphatidic Acid Metabolism and Signaling.ACS central science · 2024Article
- Phospholipase D1 produces phosphatidic acid at sites of secretory vesicle docking and fusion.Molecular biology of the cell · 2024Article
- Activation of MAPK-mediated immunity by phosphatidic acid in response to positive-strand RNA viruses.Plant communications · 2024Article
- mTORC1 is required for differentiation of germline stem cells in the Drosophila melanogaster testis.PloS one · 2024Article
- Decreased Expression of PLD2 Promotes EMT in Colorectal Cancer Invasion and Metastasis.Journal of Cancer · 2024Article
21 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
Abstract
The Ras-extracellular signal-regulated kinase (ERK) cascade is an important signaling module in cells. One regulator of the Ras-ERK cascade is phosphatidic acid (PA) generated by phospholipase D (PLD) and diacylglycerol kinase (DGK). Using a newly developed PA biosensor, PASS (phosphatidic acid biosensor with superior sensitivity), we found that PA was generated sequentially by PLD and DGK in epidermal growth factor (EGF)-stimulated HCC1806 breast cancer cells. Inhibition of PLD2, one of the two PLD members, was sufficient to eliminate most of the PA production, whereas inhibition of DGK decreased PA production only at the later stages of EGF stimulation, suggesting that PLD2 precedes DGK activation. The temporal production of PA by PLD2 is important for the nuclear activation of ERK. While inhibition of both PLD and DGK had no effect on the overall ERK activity, inhibition of PLD2 but not PLD1 or DGK blocked the nuclear ERK activity in several cancer cell lines. The decrease of active ERK in the nucleus inhibited the activation of Elk1, c-fos, and Fra1, the ERK nuclear targets, leading to decreased proliferation of HCC1806 cells. Together, these findings reveal that PA production by PLD2 determines the output of ERK in cancer cell growth factor signaling.
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