ArticleThe Journal of biological chemistry2009
A conserved serine residue is required for the phosphatidate phosphatase activity but not the transcriptional coactivator functions of lipin-1 and lipin-2.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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Who cites it
90 citing papers in PubMed, 136 citations in OpenAlex.
- [Genetic basis of chronic nonbacterial osteomyelitis].Zeitschrift fur Rheumatologie · 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
- Fatty acid metabolism and lipid channeling in macrophages: mechanisms of inflammation, resolution, and lipotoxicity.Frontiers in immunology · 2026Review
- Integrated Transcriptomic and Metabolomic Analysis of the Mechanism of Intramuscular Fat Differences in Wandong Cattle.International journal of molecular sciences · 2025Article
- Lipin phosphatidic acid phosphatases: Structure, function, regulation, and disease association.Advances in biological regulation · 2025Review
- TiORegenerative biomaterials · 2025Article
- Clinical and genetic analysis of Majeed syndrome caused by LPIN2 complex heterozygous mutation and literature review.Frontiers in pediatrics · 2025Article
- Role of LIPIN 1 in regulating metabolic homeostasis in the retinal pigment epithelium.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- IL-1 blocking experience in a case with Majeed syndrome diagnosed in adulthood.Zeitschrift fur Rheumatologie · 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
- Role of lipins in cardiovascular diseases.Lipids in health and disease · 2023Review
- Scatter Irradiation of Rat Brain Triggers Sex- and Brain Region-Specific Changes in the Expression of Non-Coding RNA Fragments.Epigenomes · 2022Article
- Betulin Targets Lipin1/2-Meidated P2X7 Receptor as a Therapeutic Approach to Attenuate Lipid Accumulation and Metaflammation.Biomolecules & therapeutics · 2022Article
- Metabolic reprogramming: A novel therapeutic target in diabetic kidney disease.Frontiers in pharmacology · 2022Review
- Sequence Variation in the Bovine Lipin-1 Gene (Animals : an open access journal from MDPI · 2021Article
- Lipin 1 modulates mRNA splicing during fasting adaptation in liver.JCI insight · 2021Article
- The middle lipin domain adopts a membrane-binding dimeric protein fold.Nature communications · 2021Article
- Lipin-1, a Versatile Regulator of Lipid Homeostasis, Is a Potential Target for Fighting Cancer.International journal of molecular sciences · 2021Review
- Deficiency of Lipin2 Results in Enhanced NF-κB Signaling and Osteoclast Formation in RAW-D Murine Macrophages.International journal of molecular sciences · 2021Article
- Majeed Syndrome: A Review of the Clinical, Genetic and Immunologic Features.Biomolecules · 2021Review
30 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Mammalian lipins (lipin-1, lipin-2, and lipin-3) are Mg2+-dependent phosphatidate phosphatase (PAP) enzymes, which catalyze a key reaction in glycerolipid biosynthesis. Lipin-1 also functions as a transcriptional coactivator in conjunction with members of the peroxisome proliferator-activated receptor family. An S734L mutation in LPIN2 causes Majeed syndrome, a human inflammatory disorder characterized by recurrent osteomyelitis, fever, dyserythropoietic anemia, and cutaneous inflammation. Here we demonstrate that mutation of the equivalent serine in mouse lipin-1 and lipin-2 to leucine or aspartate abolishes PAP activity but does not impair lipin association with microsomal membranes, the major site of glycerolipid synthesis. We also determined that lipin-2 has transcriptional coactivator activity for peroxisome proliferator-activated receptor-response elements similar to lipin-1 and that this activity is not affected by mutating the conserved serine. Therefore, our results indicate that the symptoms of the Majeed syndrome result from a loss of lipin-2 PAP activity. To characterize sites of lipin-2 action, we detected lipin-2 expression by in situ hybridization on whole mouse sections and by quantitative PCR of tissues relevant to Majeed syndrome. Lipin-2 was most prominently expressed in liver, where levels were much higher than lipin-1, and also in kidney, lung, gastrointestinal tract, and specific regions of the brain. Lipin-2 was also expressed in circulating red blood cells and sites of lymphopoiesis (bone marrow, thymus, and spleen). These results raise the possibility that the loss of lipin-2 PAP activity in erythrocytes and lymphocytes may contribute to the anemia and inflammation phenotypes observed in Majeed syndrome patients.
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