Amino acid metabolites that regulate G protein signaling during osmotic stress

James P. Shellhammer, Elizabeth Morin-Kensicki, Jacob P. Matson, Guowei Yin, Daniel G. Isom, Sharon L. Campbell, Robert P. Mohney, Henrik G. Dohlman

Research output: Contribution to journalArticle

9 Scopus citations


All cells respond to osmotic stress by implementing molecular signaling events to protect the organism. Failure to properly adapt can lead to pathologies such as hypertension and ischemia-reperfusion injury. Mitogen-activated protein kinases (MAPKs) are activated in response to osmotic stress, as well as by signals acting through G protein-coupled receptors (GPCRs). For proper adaptation, the action of these kinases must be coordinated. To identify second messengers of stress adaptation, we conducted a mass spectrometry-based global metabolomics profiling analysis, quantifying nearly 300 metabolites in the yeast S. cerevisiae. We show that three branched-chain amino acid (BCAA) metabolites increase in response to osmotic stress and require the MAPK Hog1. Ectopic addition of these BCAA derivatives promotes phosphorylation of the G protein α subunit and dampens G protein-dependent transcription, similar to that seen in response to osmotic stress. Conversely, genetic ablation of Hog1 activity or the BCAA-regulatory enzymes leads to diminished phosphorylation of Gα and increased transcription. Taken together, our results define a new class of candidate second messengers that mediate cross talk between osmotic stress and GPCR signaling pathways.

Original languageEnglish (US)
Article numbere1006829
JournalPLoS genetics
Issue number5
StatePublished - May 2017

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

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    Shellhammer, J. P., Morin-Kensicki, E., Matson, J. P., Yin, G., Isom, D. G., Campbell, S. L., Mohney, R. P., & Dohlman, H. G. (2017). Amino acid metabolites that regulate G protein signaling during osmotic stress. PLoS genetics, 13(5), [e1006829].