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...
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MDPI AG
2021-11-01
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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. |
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issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-10T05:24:59Z |
publishDate | 2021-11-01 |
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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 |
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