Evidence map›Paper›PMID 23619294›Full record

Trial reportJournal of molecular and cellular cardiology2013

Characterization of the cardiac myosin binding protein-C phosphoproteome in healthy and failing human hearts.

Viola Kooij, Ronald J Holewinski, Anne M Murphy, Jennifer E Van Eyk

Open access · greenAbstract readClinical TrialMulticenter Study
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
7.3field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

49 citing papers in PubMed, 75 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Hypertrophic cardiomyopathy inThe journal of cardiovascular aging · 2024
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  12. Review
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  15. Increased myocyte calcium sensitivity in end-stage pediatric dilated cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2019
    Article
  16. Article
  17. Article
  18. Article
  19. Cyclic Nucleotide-Directed Protein Kinases in Cardiovascular Inflammation and Growth.Journal of cardiovascular development and disease · 2018
    Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Viola KooijDepartment of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
Ronald J Holewinski
Anne M Murphy
Jennifer E Van Eyk
Johns Hopkins Medicine · USJohns Hopkins University · US

Funding

Pathobiology of Cardiac Dyssynchrony &ResynchronizationP01HL077180 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI KASS, DAVID ALAN · 2004 to 2014
$22.8M
MOLECULAR PHYSIOLOGY OF MYOCARDIAL TROPONIN I VARIANTSR01HL063038 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI MURPHY, ANNE M · 1999 to 2018
$6.2M
NHLBI PROTEOMICS INITIATIVE-N01HV28180-268028180-268028180N01HV028180 · HV · JOHNS HOPKINS UNIVERSITY · PI VAN EYK, JENNIFER E · 2002 to 2006
–
NHLBI NIH HHS HHSN268201000032CNHLBI NIH HHS N01 HV028180NHLBI NIH HHS P01 HL077180NHLBI NIH HHS R01 HL063038NHLBI NIH HHS R01 HL63038
6 · The paper itself

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.

Indexed as

AnimalsCarrier ProteinsFemaleHeart FailureHumansMaleMiceMuscle ProteinsMyocardiumMyosin Binding Protein CPhosphoproteinsPhosphorylationProtein KinasesProteomeCarrier ProteinsMuscle ProteinsMyosin Binding Protein CPhosphoproteinsProtein KinasesProteome

Identifiers

PMID23619294
PMCPMC3710717
OpenAlexW2047500774

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.