Research Article

In vivo brain GPCR signaling elucidated by phosphoproteomics

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Science  22 Jun 2018:
Vol. 360, Issue 6395, eaao4927
DOI: 10.1126/science.aao4927

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Mechanisms of drug action

Advanced mass spectrometry methods enable monitoring of tens of thousands of phosphorylation sites in proteins. This technology can potentially distinguish cellular signaling pathways that produce beneficial effects from those that produce unwanted side effects. Liu et al. treated mice with various agonists of the kappa opioid receptor (a G protein–coupled receptor) and monitored changes in phosphorylation over time in different brain regions. The phosphorylation patterns revealed distinct patterns of signaling in various brain tissues, some of which were associated with unwanted side effects.

Science, this issue p. eaao4927