ArticleThe Journal of biological chemistry2013
Regulation of phospholipase D activity and phosphatidic acid production after purinergic (P2Y6) receptor stimulation.
Article in The Journal of biological chemistry, 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, 28 citations in OpenAlex.
- Article
- Article
- Lipocalin 2 regulates mitochondrial phospholipidome remodeling, dynamics, and function in brown adipose tissue in male mice.Nature communications · 2023Article
- Acyl chain selection couples the consumption and synthesis of phosphoinositides.The EMBO journal · 2022Article
- Discovery of Phospholipase D Inhibitors with Improved Drug-like Properties and Central Nervous System Penetrance.ACS medicinal chemistry letters · 2022Article
- Mammalian phospholipase D: Function, and therapeutics.Progress in lipid research · 2020Review
- Phosphatidylinositol 4-phosphate is a major source of GPCR-stimulated phosphoinositide production.Science signaling · 2018Article
- Targeting phospholipase D in cancer, infection and neurodegenerative disorders.Nature reviews. Drug discovery · 2017Review
- Measuring Phospholipase D Enzymatic Activity Through Biochemical and Imaging Methods.Methods in enzymology · 2017Article
- Human phospholipase D activity transiently regulates pyrimidine biosynthesis in malignant gliomas.ACS chemical biology · 2015Article
- The molecular basis of leukocyte adhesion involving phosphatidic acid and phospholipase D.The Journal of biological chemistry · 2014Article
- Phospholipase D signaling pathways and phosphatidic acid as therapeutic targets in cancer.Pharmacological reviews · 2014Review
- Phospholipase D facilitates efficient entry of influenza virus, allowing escape from innate immune inhibition.The Journal of biological chemistry · 2014Article
- Chemical modulation of glycerolipid signaling and metabolic pathways.Biochimica et biophysica acta · 2014Review
- Phospholipase D2 mediates survival signaling through direct regulation of Akt in glioblastoma cells.The Journal of biological chemistry · 2014Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Phosphatidic acid (PA) is a lipid second messenger located at the intersection of several lipid metabolism and cell signaling events including membrane trafficking, survival, and proliferation. Generation of signaling PA has long been primarily attributed to the activation of phospholipase D (PLD). PLD catalyzes the hydrolysis of phosphatidylcholine into PA. A variety of both receptor-tyrosine kinase and G-protein-coupled receptor stimulations have been shown to lead to PLD activation and PA generation. This study focuses on profiling the PA pool upon P2Y6 receptor signaling manipulation to determine the major PA producing enzymes. Here we show that PLD, although highly active, is not responsible for the majority of stable PA being produced upon UDP stimulation of the P2Y6 receptor and that PA levels are tightly regulated. By following PA flux in the cell we show that PLD is involved in an initial increase in PA upon receptor stimulation; however, when PLD is blocked, the cell compensates by increasing PA production from other sources. We further delineate the P2Y6 signaling pathway showing that phospholipase Cβ3 (PLCβ3), PLCδ1, DGKζ and PLD are all downstream of receptor activation. We also show that DGKζ is a novel negative regulator of PLD activity in this system that occurs through an inhibitory mechanism with PKCα. These results further define the downstream events resulting in PA production in the P2Y6 receptor signaling pathway.
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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.