Trial reportJournal of molecular and cellular cardiology2013
Characterization of the cardiac myosin binding protein-C phosphoproteome in healthy and failing human hearts.
Trial report in Journal of molecular and cellular cardiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 75 citations in OpenAlex.
- Myocardial phosphoproteomics unveils a key role of DYRK1A in aortic valve replacement-induced reverse remodelling.Basic research in cardiology · 2025Article
- Spatially resolving how cMyBP-C phosphorylation and haploinsufficiency in porcine and human myofibrils affect β-cardiac myosin activity.The Journal of general physiology · 2025Article
- Bringing into focus the central domains C3-C6 of myosin binding protein C.Frontiers in physiology · 2024Review
- Hypertrophic cardiomyopathy inThe journal of cardiovascular aging · 2024Article
- Molecular characterization of linker and loop-mediated structural modulation and hinge motion in the C4-C5 domains of cMyBPC.Journal of structural biology · 2022Article
- Article
- Modulation of myosin by cardiac myosin binding protein-C peptides improves cardiac contractility in ex-vivo experimental heart failure models.Scientific reports · 2022Article
- Titin-truncating mutations associated with dilated cardiomyopathy alter length-dependent activation and its modulation via phosphorylation.Cardiovascular research · 2022Article
- Long-Term PDE-5A Inhibition Improves Myofilament Function in Left and Right Ventricular Cardiomyocytes through Partially Different Mechanisms in Diabetic Rat Hearts.Antioxidants (Basel, Switzerland) · 2021Article
- The Interplay between S-Glutathionylation and Phosphorylation of Cardiac Troponin I and Myosin Binding Protein C in End-Stage Human Failing Hearts.Antioxidants (Basel, Switzerland) · 2021Article
- cMyBPC phosphorylation modulates the effect of omecamtiv mecarbil on myocardial force generation.The Journal of general physiology · 2021Article
- Genetic, clinical, molecular, and pathogenic aspects of the South Asian-specific polymorphic MYBPC3Biophysical reviews · 2020Review
- Late-life restoration of mitochondrial function reverses cardiac dysfunction in old mice.eLife · 2020Article
- A Novel "Cut and Paste" Method for In Situ Replacement of cMyBP-C Reveals a New Role for cMyBP-C in the Regulation of Contractile Oscillations.Circulation research · 2020Article
- Increased myocyte calcium sensitivity in end-stage pediatric dilated cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2019Article
- Cardiac Myosin Binding Protein-C Phosphorylation Mitigates Age-Related Cardiac Dysfunction: Hope for Better Aging?JACC. Basic to translational science · 2019Article
- MYBPC3 truncation mutations enhance actomyosin contractile mechanics in human hypertrophic cardiomyopathy.Journal of molecular and cellular cardiology · 2019Article
- Data on whole length myosin binding protein C stabilizes myosin S2 as measured by gravitational force spectroscopy.Data in brief · 2018Article
- Cyclic Nucleotide-Directed Protein Kinases in Cardiovascular Inflammation and Growth.Journal of cardiovascular development and disease · 2018Review
- Functional communication between PKC-targeted cardiac troponin I phosphorylation sites.Archives of biochemistry and biophysics · 2017Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
introductionCardiac myosin binding protein-C (cMyBP-C) becomes dephosphorylated in the failing heart and reduced phosphorylation-dependent regulation of cMyBP-C has been implicated in contractile dysfunction. To date, several phosphorylation sites have been identified for human cMyBP-C; however, a comprehensive characterization of the cMyBP-C phosphoproteome is lacking. This study aimed to characterize the cMyBP-C phosphoproteome using two different proteomic-based methods in explanted donor and end-stage failing hearts.
methodsThe first approach used to characterize the cMyBP-C phosphoproteome employed a strong-cation exchange chromatography (SCX) fractionation method (10 pooled samples, technical replicates=4) and the second employed a sodium dodecylsulfate polyacrylamide gel electrophoresis method (n=10; technical replicates=2). Each subsequently underwent titanium dioxide (TiO2) affinity chromatography to enrich for the tryptic phosphopeptides, which were analyzed using an LTQ-Orbitrap mass spectrometer. Moreover, recombinant C0-C2 fragment of mouse cMyBP-C incubated with PKA, PKC, CaMKII and CK2 was analyzed to identify the kinases involved with phosphorylation of cMyBP-C.
resultsSeventeen phosphorylation sites on cMyBP-C were identified in vivo, with the majority localized in the N-terminal domains C0-C2. The three most abundant phosphorylated sites, Ser284, Ser286 and Thr290, are located in the regulatory M-domain of cMyBP-C. Ser284 showed a significant reduction in phosphorylation in HF.
conclusionThis study demonstrates that cMyBP-C harbors more phosphorylation sites than previously known, with a total of 17 (9 novel) identified phosphorylation sites in vivo. Most sites were primarily located within the N-terminal side of the protein. The most highly phosphorylated site on cMyBP-C was Ser284 and this site showed decreased phosphorylation in the failing heart, which implicates importance for fine-tuning contractility. To date, the functional importance of Ser286 and Thr290 is unknown. In addition, 16 sites were identified after in vitro kinase incubation. The data have been deposited to the ProteomeXchange with identifier PXD000158.
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