ArticleThe Journal of biological chemistry2011
The inhibitory effect of phospholemman on the sodium pump requires its palmitoylation.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 76 citations in OpenAlex.
- Protein lipidation in cardiovascular homeostasis, development, and disease.Clinical science (London, England : 1979) · 2026Review
- Post-translational modifications of na+/K+-atpase subunits: regulatory mechanisms and functional implications.Frontiers in cell and developmental biology · 2026Review
- Protein palmitoylation: A potential therapeutic target in cardiovascular diseases.Acta pharmaceutica Sinica. B · 2025Review
- Palmitic acid and palmitoylation in cancer: Understanding, insights, and challenges.Innovation (Cambridge (Mass.)) · 2025Review
- Mechanisms and functional implications of ZDHHC5 in cellular physiology and disease.Journal of lipid research · 2025Review
- Nanobody-thioesterase chimeras to specifically target protein palmitoylation.Nature communications · 2025Article
- scRNA-seq reveals the diversity of the developing cardiac cell lineage and molecular players in heart rhythm regulation.iScience · 2024Article
- Regulation of cardiomyocyte intracellular trafficking and signal transduction by protein palmitoylation.Biochemical Society transactions · 2024Article
- Article
- ATP1A1-linked diseases require a malfunctioning protein product from one allele.Biochimica et biophysica acta. Molecular cell research · 2024Article
- Palmitoylation of the pore-forming subunit of Ca(v)1.2 controls channel voltage sensitivity and calcium transients in cardiac myocytes.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Palmitoylation regulates the magnitude of HCN4-mediated currents in mammalian cells.Frontiers in physiology · 2023Article
- Dynamic but discordant alterations in zDHHC5 expression and palmitoylation of its substrates in cardiac pathologies.Frontiers in physiology · 2022Article
- FXYD proteins and sodium pump regulatory mechanisms.The Journal of general physiology · 2021Review
- Phospholemman Phosphorylation Regulates Vascular Tone, Blood Pressure, and Hypertension in Mice and Humans.Circulation · 2021Article
- Regulation of Dynamic Protein S-Acylation.Frontiers in molecular biosciences · 2021Review
- Putative Role of Protein Palmitoylation in Cardiac Lipid-Induced Insulin Resistance.International journal of molecular sciences · 2020Review
- FXYD protein isoforms differentially modulate human Na/K pump function.The Journal of general physiology · 2020Article
- Control of protein palmitoylation by regulating substrate recruitment to a zDHHC-protein acyltransferase.Communications biology · 2020Article
- DHHC5 Mediates β-Adrenergic Signaling in Cardiomyocytes by Targeting Gα Proteins.Biophysical journal · 2020Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Phospholemman (PLM), the principal sarcolemmal substrate for protein kinases A and C in the heart, regulates the cardiac sodium pump. We investigated post-translational modifications of PLM additional to phosphorylation in adult rat ventricular myocytes (ARVM). LC-MS/MS of tryptically digested PLM immunoprecipitated from ARVM identified cysteine 40 as palmitoylated in some peptides, but no information was obtained regarding the palmitoylation status of cysteine 42. PLM palmitoylation was confirmed by immunoprecipitating PLM from ARVM loaded with [(3)H]palmitic acid and immunoblotting following streptavidin affinity purification from ARVM lysates subjected to fatty acyl biotin exchange. Mutagenesis identified both Cys-40 and Cys-42 of PLM as palmitoylated. Phosphorylation of PLM at serine 68 by PKA in ARVM or transiently transfected HEK cells increased its palmitoylation, but PKA activation did not increase the palmitoylation of S68A PLM-YFP in HEK cells. Wild type and unpalmitoylatable PLM-YFP were all correctly targeted to the cell surface membrane, but the half-life of unpalmitoylatable PLM was reduced compared with wild type. In cells stably expressing inducible PLM, PLM expression inhibited the sodium pump, but PLM did not inhibit the sodium pump when palmitoylation was inhibited. Hence, palmitoylation of PLM controls its turnover, and palmitoylated PLM inhibits the sodium pump. Surprisingly, phosphorylation of PLM enhances its palmitoylation, probably through the enhanced mobility of the phosphorylated intracellular domain increasing the accessibility of cysteines for the palmitoylating enzyme, with interesting theoretical implications. All FXYD proteins have conserved intracellular cysteines, so FXYD protein palmitoylation may be a universal means to regulate the sodium pump.
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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.