Research ResourceBiochemistry

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

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Sci. Signal.  04 Jun 2013:
Vol. 6, Issue 278, pp. rs11
DOI: 10.1126/scisignal.2003506

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Getting to the Heart of Signaling

Patients with high blood pressure and other heart-related conditions routinely take inhibitors of β-adrenergic receptors (βARs) to prevent cardiac dysfunction. βAR signaling leads to the increased contractility of cardiomyocytes, among other effects; however, the number of downstream targets of βARs is unclear. Lundby et al. treated mice with combinations of specific β1AR and β2AR agonists and antagonists to activate each receptor isoform individually before harvesting the hearts and subjecting them to phosphoproteomics analysis. The authors identified previously uncharacterized peptides and sites phosphorylated in response to β1AR signaling, as well as characterized the activation of a potassium channel important for increasing heart rate. This in vivo approach provides insights into βAR signaling pathways that may help in understanding how heart diseases develop and how they may be treated.