ArticleThe Journal of biological chemistry2013
Phosphorylation of lipin 1 and charge on the phosphatidic acid head group control its phosphatidic acid phosphatase activity and membrane association.
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 61 papers.
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Who cites it
61 citing papers in PubMed, 96 citations in OpenAlex.
- Targeting the GSK-3β/mTOR axis: a novel pharmacological strategy for preeclampsia prevention and treatment.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- A fluorescence and HPLC-based activity assay system for lipid-modifying enzymes: Lipin/Pah phosphatidic acid phosphatase as an optimized example.Methods in enzymology · 2026Article
- Persistent mTORC1 activation underlies sex dimorphic progression of MASLD in mice with hepatocyte prohibitin-1 deficiency.Research square · 2025Article
- Investigating Network and Experimental Effect of Silibinin on Lipin-1 and Lipin-2 Gene Expression during Ischemia-reperfusion of the Liver in Rats.Cell biochemistry and biophysics · 2025Article
- Lipin phosphatidic acid phosphatases: Structure, function, regulation, and disease association.Advances in biological regulation · 2025Review
- Lipin-1 restrains macrophage lipid synthesis to promote inflammation resolution.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Architecture and function of yeast phosphatidate phosphatase Pah1 domains/regions.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2024Review
- Phosphatidylserine enrichment in the nuclear membrane regulates key enzymes of phosphatidylcholine synthesis.The EMBO journal · 2024Article
- Structure and mechanism of the human CTDNEP1-NEP1R1 membrane protein phosphatase complex necessary to maintain ER membrane morphology.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Research Progress on the Mechanism of Milk Fat Synthesis in Cows and the Effect of Conjugated Linoleic Acid on Milk Fat Metabolism and Its Underlying Mechanism: A Review.Animals : an open access journal from MDPI · 2024Review
- The Saccharomyces cerevisiae Spo7 basic tail is required for Nem1-Spo7/Pah1 phosphatase cascade function in lipid synthesis.The Journal of biological chemistry · 2024Article
- LPIN2 is the phosphatase dominating the penultimate step of neutral lipid biosynthesis inmicroPublication biology · 2024Article
- Structure and mechanism of the human CTDNEP1-NEP1R1 membrane protein phosphatase complex necessary to maintain ER membrane morphology.bioRxiv : the preprint server for biology · 2023Article
- Role of lipins in cardiovascular diseases.Lipids in health and disease · 2023Review
- Lipin-1 restrains macrophage lipid synthesis to promote inflammation resolution.bioRxiv : the preprint server for biology · 2023Article
- Malonyl-CoA is a conserved endogenous ATP-competitive mTORC1 inhibitor.Nature cell biology · 2023Article
- Coupling lipid synthesis with nuclear envelope remodeling.Trends in biochemical sciences · 2022Review
- Selectivity of mTOR-Phosphatidic Acid Interactions Is Driven by Acyl Chain Structure and Cholesterol.Cells · 2021Article
- Cell cycle regulation of ER membrane biogenesis protects against chromosome missegregation.Developmental cell · 2021Article
- Lipin-1-derived diacylglycerol activates intracellular TRPC3 which is critical for inflammatory signaling.Cellular and molecular life sciences : CMLS · 2021Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
The lipin gene family encodes a class of Mg(2+)-dependent phosphatidic acid phosphatases involved in the de novo synthesis of phospholipids and triglycerides. Unlike other enzymes in the Kennedy pathway, lipins are not integral membrane proteins, and they need to translocate from the cytosol to intracellular membranes to participate in glycerolipid synthesis. The movement of lipin 1 within the cell is closely associated with its phosphorylation status. Although cellular analyses have demonstrated that highly phosphorylated lipin 1 is enriched in the cytosol and dephosphorylated lipin 1 is found on membranes, the effects of phosphorylation on lipin 1 activity and binding to membranes has not been recapitulated in vitro. Herein we describe a new biochemical assay for lipin 1 using mixtures of phosphatidic acid (PA) and phosphatidylethanolamine that reflects its physiological activity and membrane interaction. This depends on our observation that lipin 1 binding to PA in membranes is highly responsive to the electrostatic charge of PA. The studies presented here demonstrate that phosphorylation regulates the ability of the polybasic domain of lipin 1 to recognize di-anionic PA and identify mTOR as a crucial upstream signaling component regulating lipin 1 phosphorylation. These results demonstrate how phosphorylation of lipin 1 together with pH and membrane phospholipid composition play important roles in the membrane association of lipin 1 and thus the regulation of its enzymatic activity.
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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.