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

International Journal of Molecular Sciences

Henning Urlaub¹  Kuan-Ting Pan¹  Pan Fang¹  Yanlong Ji¹  Christof Lenz¹  Alican Güran²  Metin Avkiran² 

[1] Bioanalytical Mass Spectrometry Group, Max Planck Institute for Biophysical Chemistry, 37077 Goettingen, Germany;British 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, UK;

关键词: phosphorylation;    cell signalling;    mass spectrometry;    β-adrenergic receptor;    SILAC;   

DOI  :  10.3390/ijms222212584

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown