{"doi":"10.17615/b5xj-qj51","title":"Amino acid metabolites that regulate G protein signaling during osmotic stress","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.","journal":"UNC Libraries","year":2020,"id":136705,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9509,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":397056,"name":"Sharon L. Campbell","orcid":"0000-0003-0311-409X","position":1,"is_corresponding":false},{"id":406789,"name":"Henrik Dohlman","orcid":"0000-0003-2443-0729","position":2,"is_corresponding":false},{"id":535397,"name":"Elizabeth Morin‐Kensicki","orcid":"0000-0003-4653-5943","position":3,"is_corresponding":false},{"id":397051,"name":"Guowei Yin","orcid":"0000-0003-2669-7160","position":4,"is_corresponding":false},{"id":596460,"name":"James P. Shellhammer","orcid":null,"position":5,"is_corresponding":false},{"id":51058,"name":"Robert P. Mohney","orcid":"0000-0002-9315-9541","position":6,"is_corresponding":false},{"id":430590,"name":"Jacob P. Matson","orcid":"0000-0002-9375-1676","position":7,"is_corresponding":false},{"id":304965,"name":"Daniel G. Isom","orcid":"0000-0001-5637-2370","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:16:52.487376Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}