ArticleThe Journal of biological chemistry2012
Lethal, hereditary mutants of phospholamban elude phosphorylation by protein kinase A.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
37 citing papers in PubMed, 2 syntheses or guidelines pooled it, 65 citations in OpenAlex.
- ACMG SF v3.3 list for reporting of secondary findings in clinical exome and genome sequencing: A policy statement of the American College of Medical Genetics and Genomics (ACMG).Genetics in medicine : official journal of the American College of Medical Genetics · 2025Guideline
- Protein Phosphorylation Alterations in Myotonic Dystrophy Type 1: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Promoting Autophagy Mitigates Stress-Induced Remodeling in Patient iPSC-CMs with the Phospholamban R9C Mutation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Microprotein, macro-effect: DWORF as a therapeutic strategy in heart failure.Frontiers in cell and developmental biology · 2026Review
- In PLN-R14del mice, SR structure restoration, rather than calcium cycling, is the dominant effector of PLN-ASO treatment.Cardiovascular research · 2025Article
- Genetic landscape of phospholamban cardiomyopathies.Frontiers in cell and developmental biology · 2025Review
- Novel Copy Number Deletion InvolvingClinical case reports · 2025Article
- Cardiac Applications of CRISPR/AAV-Mediated Precise Genome Editing.bioRxiv : the preprint server for biology · 2024Article
- Pathological mutations in the phospholamban cytoplasmic region affect its topology and dynamics modulating the extent of SERCA inhibition.Biochimica et biophysica acta. Biomembranes · 2024Article
- Phospholamban pentamerization increases sensitivity and dynamic range of cardiac relaxation.Cardiovascular research · 2023Article
- Phospholamban R14del disease: The past, the present and the future.Frontiers in cardiovascular medicine · 2023Review
- Structures of PKA-phospholamban complexes reveal a mechanism of familial dilated cardiomyopathy.eLife · 2022Article
- Review
- Arrhythmia Mechanism and Dynamics in a Humanized Mouse Model of Inherited Cardiomyopathy Caused by Phospholamban R14del Mutation.Circulation · 2021Article
- Variant Interpretation for Dilated Cardiomyopathy: Refinement of the American College of Medical Genetics and Genomics/ClinGen Guidelines for the DCM Precision Medicine Study.Circulation. Genomic and precision medicine · 2020Article
- Interaction of a Sarcolipin Pentamer and Monomer with the Sarcoplasmic Reticulum Calcium Pump, SERCA.Biophysical journal · 2020Article
- RNA-seq analysis identifies cytoskeletal structural genes and pathways for meat quality in beef.PloS one · 2020Article
- Thermodynamics of Cation Binding to the Sarcoendoplasmic Reticulum Calcium ATPase Pump and Impacts on Enzyme Function.Journal of chemical theory and computation · 2019Article
- Alterations of protein expression of phospholamban, ZASP and plakoglobin in human atria in subgroups of seniors.Scientific reports · 2019Article
- PKC and PKN in heart disease.Journal of molecular and cellular cardiology · 2019Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The sarcoplasmic reticulum calcium pump (SERCA) and its regulator, phospholamban, are essential components of cardiac contractility. Phospholamban modulates contractility by inhibiting SERCA, and this process is dynamically regulated by β-adrenergic stimulation and phosphorylation of phospholamban. Herein we reveal mechanistic insight into how four hereditary mutants of phospholamban, Arg(9) to Cys, Arg(9) to Leu, Arg(9) to His, and Arg(14) deletion, alter regulation of SERCA. Deletion of Arg(14) disrupts the protein kinase A recognition motif, which abrogates phospholamban phosphorylation and results in constitutive SERCA inhibition. Mutation of Arg(9) causes more complex changes in function, where hydrophobic substitutions such as cysteine and leucine eliminate both SERCA inhibition and phospholamban phosphorylation, whereas an aromatic substitution such as histidine selectively disrupts phosphorylation. We demonstrate that the role of Arg(9) in phospholamban function is multifaceted: it is important for inhibition of SERCA, it increases the efficiency of phosphorylation, and it is critical for protein kinase A recognition in the context of the phospholamban pentamer. Given the synergistic consequences on contractility, it is not surprising that the mutants cause lethal, hereditary dilated cardiomyopathy.
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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.