{"controller"=>"catalog", "action"=>"show", "id"=>"242119723"}
  • EN
  • DA

Danish NationalResearch Database

  • Search Publications & Researchers
  • Open Access Indicator
  • Publications
  • Researchers
Example Finds records
water{} containing the word "water".
water supplies"{}" containing the phrase "water supplies".
author:"Doe, John"author:"{}" containing the prase "Doe, John" in the author field.
title:IEEEtitle:{} containing the word "IEEE" in the title field.
Need more help? Advanced search tutorial
  • Selected (0)
  • History

In Vivo Phosphoproteomics Analysis Reveals the Cardiac Targets of β-Adrenergic Receptor Signaling

    • Save to Mendeley
    • Export to BibTeX
    • Export to RIS
    • Email citation
Authors:
  • Lundby, Alicia ;
    Close
    Orcid logo0000-0002-1612-6041
    Proteomics Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, Københavns Universitet
  • Andersen, Martin N ;
    Close
    Heart, Renal and Circulation, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet
  • Steffensen, Annette B ;
    Close
    ICMM Section 8, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
  • Horn, Heiko ;
    Close
    Disease Systems Biology Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, Københavns Universitet
  • Kelstrup, Christian D ;
    Close
    Orcid logo0000-0003-4647-1425
    Proteomics Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, Københavns Universitet
  • Francavilla, Chiara ;
    Close
    Proteomics Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, Københavns Universitet
  • Jensen, Lars J ;
    Close
    Orcid logo0000-0001-7885-715X
    Disease Systems Biology Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, Københavns Universitet
  • Schmitt, Nicole ;
    Close
    Orcid logo0000-0001-9482-9749
    Molecular Cardiology and Membrane Proteins, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet
  • Thomsen, Morten B ;
    Close
    Orcid logo0000-0002-2469-6458
    Heart, Renal and Circulation, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet
  • Olsen, Jesper V
    Close
    Orcid logo0000-0002-4747-4938
    Proteomics Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, Københavns Universitet
DOI:
10.1126/scisignal.2003506
Abstract:
β-Blockers are widely used to prevent cardiac arrhythmias and to treat hypertension by inhibiting β-adrenergic receptors (βARs) and thus decreasing contractility and heart rate. βARs initiate phosphorylation-dependent signaling cascades, but only a small number of the target proteins are known. We used quantitative in vivo phosphoproteomics to identify 670 site-specific phosphorylation changes in murine hearts in response to acute treatment with specific βAR agonists. The residues adjacent to the regulated phosphorylation sites exhibited a sequence-specific preference (R-X-X-pS/T), and integrative analysis of sequence motifs and interaction networks suggested that the kinases AMPK (adenosine 5'-monophosphate-activated protein kinase), Akt, and mTOR (mammalian target of rapamycin) mediate βAR signaling, in addition to the well-established pathways mediated by PKA (cyclic adenosine monophosphate-dependent protein kinase) and CaMKII (calcium/calmodulin-dependent protein kinase type II). We found specific regulation of phosphorylation sites on six ion channels and transporters that mediate increased ion fluxes at higher heart rates, and we showed that phosphorylation of one of these, Ser(92) of the potassium channel KV7.1, increased current amplitude. Our data set represents a quantitative analysis of phosphorylated proteins regulated in vivo upon stimulation of seven-transmembrane receptors, and our findings reveal previously unknown phosphorylation sites that regulate myocardial contractility, suggesting new potential targets for the treatment of heart disease and hypertension.
Type:
Journal article
Language:
English
Published in:
Science Signaling, 2013, Vol 6, Issue 278
Main Research Area:
Medical science
Publication Status:
Published
Review type:
Peer Review
Submission year:
2013
Scientific Level:
Scientific
ID:
242119723

Full text access

  • Doi Get publisher edition via DOI resolver
Checking for on-site access...

On-site access

At institution

  • Copenhagen university.en

Metrics

Feedback

Sitemap

  • Search
    • Statistics
    • Tutorial
    • Data
    • FAQ
    • Contact
  • Open Access
    • Overview
    • Development
    • FAQ
    • Contact
  • About
    • Institutions
    • Release History
    • Cookies and privacy policy

Copyright © 1998–2018.

Fivu en