Quantitative Analysis of the Cardiac Phosphoproteome in Response to Acute β-Adrenergic Receptor Stimulation In Vivo

β-adrenergic receptor (β-AR) stimulation represents a major mechanism of modulating cardiac output. In spite of its fundamental importance, its molecular basis on the level of cell signalling has not been characterised in detail yet. We employed mass spectrometry-based proteome and phosphoproteome a...

Full description

Bibliographic Details
Main Authors: Alican Güran, Yanlong Ji, Pan Fang, Kuan-Ting Pan, Henning Urlaub, Metin Avkiran, Christof Lenz
Format: Article
Language:English
Published: MDPI AG 2021-11-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/22/12584
_version_ 1797509950911545344
author Alican Güran
Yanlong Ji
Pan Fang
Kuan-Ting Pan
Henning Urlaub
Metin Avkiran
Christof Lenz
author_facet Alican Güran
Yanlong Ji
Pan Fang
Kuan-Ting Pan
Henning Urlaub
Metin Avkiran
Christof Lenz
author_sort Alican Güran
collection DOAJ
description β-adrenergic receptor (β-AR) stimulation represents a major mechanism of modulating cardiac output. In spite of its fundamental importance, its molecular basis on the level of cell signalling has not been characterised in detail yet. We employed mass spectrometry-based proteome and phosphoproteome analysis using SuperSILAC (spike-in stable isotope labelling by amino acids in cell culture) standardization to generate a comprehensive map of acute phosphoproteome changes in mice upon administration of isoprenaline (ISO), a synthetic β-AR agonist that targets both β1-AR and β2-AR subtypes. Our data describe 8597 quantitated phosphopeptides corresponding to 10,164 known and novel phospho-events from 2975 proteins. In total, 197 of these phospho-events showed significantly altered phosphorylation, indicating an intricate signalling network activated in response to β-AR stimulation. In addition, we unexpectedly detected significant cardiac expression and ISO-induced fragmentation of junctophilin-1, a junctophilin isoform hitherto only thought to be expressed in skeletal muscle. Data are available via ProteomeXchange with identifier PXD025569.
first_indexed 2024-03-10T05:24:59Z
format Article
id doaj.art-b1c1a91be2a84b30b4b7f5302b692782
institution Directory Open Access Journal
issn 1661-6596
1422-0067
language English
last_indexed 2024-03-10T05:24:59Z
publishDate 2021-11-01
publisher MDPI AG
record_format Article
series International Journal of Molecular Sciences
spelling doaj.art-b1c1a91be2a84b30b4b7f5302b6927822023-11-22T23:44:48ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-11-0122221258410.3390/ijms222212584Quantitative Analysis of the Cardiac Phosphoproteome in Response to Acute β-Adrenergic Receptor Stimulation In VivoAlican Güran0Yanlong Ji1Pan Fang2Kuan-Ting Pan3Henning Urlaub4Metin Avkiran5Christof Lenz6British Heart Foundation Centre of Research Excellence, School of Cardiovascular Medicine and Sciences, King’s College London, St Thomas’ Hospital, Westminster Bridge Road, London SE1 7EH, UKBioanalytical Mass Spectrometry Group, Max Planck Institute for Biophysical Chemistry, 37077 Goettingen, GermanyBioanalytical Mass Spectrometry Group, Max Planck Institute for Biophysical Chemistry, 37077 Goettingen, GermanyBioanalytical Mass Spectrometry Group, Max Planck Institute for Biophysical Chemistry, 37077 Goettingen, GermanyBioanalytical Mass Spectrometry Group, Max Planck Institute for Biophysical Chemistry, 37077 Goettingen, GermanyBritish Heart Foundation Centre of Research Excellence, School of Cardiovascular Medicine and Sciences, King’s College London, St Thomas’ Hospital, Westminster Bridge Road, London SE1 7EH, UKBioanalytical Mass Spectrometry Group, Max Planck Institute for Biophysical Chemistry, 37077 Goettingen, Germanyβ-adrenergic receptor (β-AR) stimulation represents a major mechanism of modulating cardiac output. In spite of its fundamental importance, its molecular basis on the level of cell signalling has not been characterised in detail yet. We employed mass spectrometry-based proteome and phosphoproteome analysis using SuperSILAC (spike-in stable isotope labelling by amino acids in cell culture) standardization to generate a comprehensive map of acute phosphoproteome changes in mice upon administration of isoprenaline (ISO), a synthetic β-AR agonist that targets both β1-AR and β2-AR subtypes. Our data describe 8597 quantitated phosphopeptides corresponding to 10,164 known and novel phospho-events from 2975 proteins. In total, 197 of these phospho-events showed significantly altered phosphorylation, indicating an intricate signalling network activated in response to β-AR stimulation. In addition, we unexpectedly detected significant cardiac expression and ISO-induced fragmentation of junctophilin-1, a junctophilin isoform hitherto only thought to be expressed in skeletal muscle. Data are available via ProteomeXchange with identifier PXD025569.https://www.mdpi.com/1422-0067/22/22/12584phosphorylationcell signallingmass spectrometryβ-adrenergic receptorSILAC
spellingShingle Alican Güran
Yanlong Ji
Pan Fang
Kuan-Ting Pan
Henning Urlaub
Metin Avkiran
Christof Lenz
Quantitative Analysis of the Cardiac Phosphoproteome in Response to Acute β-Adrenergic Receptor Stimulation In Vivo
International Journal of Molecular Sciences
phosphorylation
cell signalling
mass spectrometry
β-adrenergic receptor
SILAC
title Quantitative Analysis of the Cardiac Phosphoproteome in Response to Acute β-Adrenergic Receptor Stimulation In Vivo
title_full Quantitative Analysis of the Cardiac Phosphoproteome in Response to Acute β-Adrenergic Receptor Stimulation In Vivo
title_fullStr Quantitative Analysis of the Cardiac Phosphoproteome in Response to Acute β-Adrenergic Receptor Stimulation In Vivo
title_full_unstemmed Quantitative Analysis of the Cardiac Phosphoproteome in Response to Acute β-Adrenergic Receptor Stimulation In Vivo
title_short Quantitative Analysis of the Cardiac Phosphoproteome in Response to Acute β-Adrenergic Receptor Stimulation In Vivo
title_sort quantitative analysis of the cardiac phosphoproteome in response to acute β adrenergic receptor stimulation in vivo
topic phosphorylation
cell signalling
mass spectrometry
β-adrenergic receptor
SILAC
url https://www.mdpi.com/1422-0067/22/22/12584
work_keys_str_mv AT alicanguran quantitativeanalysisofthecardiacphosphoproteomeinresponsetoacutebadrenergicreceptorstimulationinvivo
AT yanlongji quantitativeanalysisofthecardiacphosphoproteomeinresponsetoacutebadrenergicreceptorstimulationinvivo
AT panfang quantitativeanalysisofthecardiacphosphoproteomeinresponsetoacutebadrenergicreceptorstimulationinvivo
AT kuantingpan quantitativeanalysisofthecardiacphosphoproteomeinresponsetoacutebadrenergicreceptorstimulationinvivo
AT henningurlaub quantitativeanalysisofthecardiacphosphoproteomeinresponsetoacutebadrenergicreceptorstimulationinvivo
AT metinavkiran quantitativeanalysisofthecardiacphosphoproteomeinresponsetoacutebadrenergicreceptorstimulationinvivo
AT christoflenz quantitativeanalysisofthecardiacphosphoproteomeinresponsetoacutebadrenergicreceptorstimulationinvivo