Amino acid metabolites that regulate G protein signaling during osmotic stress.
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 we...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-05-01
|
| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC5469498?pdf=render |
| _version_ | 1818924701038149632 |
|---|---|
| author | James P Shellhammer Elizabeth Morin-Kensicki Jacob P Matson Guowei Yin Daniel G Isom Sharon L Campbell Robert P Mohney Henrik G Dohlman |
| author_facet | James P Shellhammer Elizabeth Morin-Kensicki Jacob P Matson Guowei Yin Daniel G Isom Sharon L Campbell Robert P Mohney Henrik G Dohlman |
| author_sort | James P Shellhammer |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T02:29:30Z |
| format | Article |
| id | doaj.art-e1557cf21e24484d89a2ddd935501880 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-20T02:29:30Z |
| publishDate | 2017-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-e1557cf21e24484d89a2ddd9355018802022-12-21T19:56:37ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042017-05-01135e100682910.1371/journal.pgen.1006829Amino acid metabolites that regulate G protein signaling during osmotic stress.James P ShellhammerElizabeth Morin-KensickiJacob P MatsonGuowei YinDaniel G IsomSharon L CampbellRobert P MohneyHenrik G DohlmanAll 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.http://europepmc.org/articles/PMC5469498?pdf=render |
| spellingShingle | James P Shellhammer Elizabeth Morin-Kensicki Jacob P Matson Guowei Yin Daniel G Isom Sharon L Campbell Robert P Mohney Henrik G Dohlman Amino acid metabolites that regulate G protein signaling during osmotic stress. PLoS Genetics |
| title | Amino acid metabolites that regulate G protein signaling during osmotic stress. |
| title_full | Amino acid metabolites that regulate G protein signaling during osmotic stress. |
| title_fullStr | Amino acid metabolites that regulate G protein signaling during osmotic stress. |
| title_full_unstemmed | Amino acid metabolites that regulate G protein signaling during osmotic stress. |
| title_short | Amino acid metabolites that regulate G protein signaling during osmotic stress. |
| title_sort | amino acid metabolites that regulate g protein signaling during osmotic stress |
| url | http://europepmc.org/articles/PMC5469498?pdf=render |
| work_keys_str_mv | AT jamespshellhammer aminoacidmetabolitesthatregulategproteinsignalingduringosmoticstress AT elizabethmorinkensicki aminoacidmetabolitesthatregulategproteinsignalingduringosmoticstress AT jacobpmatson aminoacidmetabolitesthatregulategproteinsignalingduringosmoticstress AT guoweiyin aminoacidmetabolitesthatregulategproteinsignalingduringosmoticstress AT danielgisom aminoacidmetabolitesthatregulategproteinsignalingduringosmoticstress AT sharonlcampbell aminoacidmetabolitesthatregulategproteinsignalingduringosmoticstress AT robertpmohney aminoacidmetabolitesthatregulategproteinsignalingduringosmoticstress AT henrikgdohlman aminoacidmetabolitesthatregulategproteinsignalingduringosmoticstress |