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 Citations (Scopus)

Abstract

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
Volume13
Issue number5
DOIs
StatePublished - May 1 2017

Fingerprint

Osmoregulation
Branched Chain Amino Acids
Osmotic Pressure
osmotic stress
G-proteins
GTP-Binding Proteins
metabolite
amino acid
branched chain amino acids
Second Messenger Systems
metabolites
G-Protein-Coupled Receptors
Mitogen-Activated Protein Kinases
Amino Acids
amino acids
protein
Phosphorylation
second messengers
Metabolomics
mitogen-activated protein kinase

ASJC Scopus subject areas

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

Cite this

Shellhammer, J. P., Morin-Kensicki, E., Matson, J. P., Yin, G., Isom, D. G., Campbell, S. L., ... Dohlman, H. G. (2017). Amino acid metabolites that regulate G protein signaling during osmotic stress. PLoS Genetics, 13(5), [e1006829]. https://doi.org/10.1371/journal.pgen.1006829

Amino acid metabolites that regulate G protein signaling during osmotic stress. / Shellhammer, James P.; Morin-Kensicki, Elizabeth; Matson, Jacob P.; Yin, Guowei; Isom, Daniel G.; Campbell, Sharon L.; Mohney, Robert P.; Dohlman, Henrik G.

In: PLoS Genetics, Vol. 13, No. 5, e1006829, 01.05.2017.

Research output: Contribution to journalArticle

Shellhammer, JP, Morin-Kensicki, E, Matson, JP, Yin, G, Isom, DG, Campbell, SL, Mohney, RP & Dohlman, HG 2017, 'Amino acid metabolites that regulate G protein signaling during osmotic stress', PLoS Genetics, vol. 13, no. 5, e1006829. https://doi.org/10.1371/journal.pgen.1006829
Shellhammer JP, Morin-Kensicki E, Matson JP, Yin G, Isom DG, Campbell SL et al. Amino acid metabolites that regulate G protein signaling during osmotic stress. PLoS Genetics. 2017 May 1;13(5). e1006829. https://doi.org/10.1371/journal.pgen.1006829
Shellhammer, James P. ; Morin-Kensicki, Elizabeth ; Matson, Jacob P. ; Yin, Guowei ; Isom, Daniel G. ; Campbell, Sharon L. ; Mohney, Robert P. ; Dohlman, Henrik G. / Amino acid metabolites that regulate G protein signaling during osmotic stress. In: PLoS Genetics. 2017 ; Vol. 13, No. 5.
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