{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T08:07:48Z","timestamp":1793779668288,"version":"4.6.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012314","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000}}],"reference-count":65,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T00:00:00Z","timestamp":1734912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/K016393\/1"],"award-info":[{"award-number":["BB\/K016393\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/P020119\/1"],"award-info":[{"award-number":["BB\/P020119\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["215599\/Z\/19\/Z"],"award-info":[{"award-number":["215599\/Z\/19\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/K017365\/1"],"award-info":[{"award-number":["BB\/K017365\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/M026663\/1"],"award-info":[{"award-number":["MR\/M026663\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/M026663\/2"],"award-info":[{"award-number":["MR\/M026663\/2"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["224323\/Z\/21\/Z"],"award-info":[{"award-number":["224323\/Z\/21\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/N006364\/1"],"award-info":[{"award-number":["MR\/N006364\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/N006364\/2"],"award-info":[{"award-number":["MR\/N006364\/2"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    The Hog1 stress-activated protein kinase (SAPK) is a key mediator of stress resistance and virulence in\n                    <jats:italic>Candida albicans<\/jats:italic>\n                    . Hog1 activation via phosphorylation of the canonical TGY motif is mediated by the Pbs2 MAPKK, which itself is activated by the Ssk2 MAPKKK. Although this three-tiered SAPK signalling module is well characterised, it is unclear how Hog1 activation is regulated in response to different stresses. Functioning upstream of the Ssk2 MAPKKK is a two-component related signal transduction system comprising three sensor histidine kinases, a phosphotransfer protein Ypd1, and a response regulator Ssk1. Here, we report that Ssk1 is a master regulator of the Hog1 SAPK that promotes stress resistance and Hog1 phosphorylation in response to diverse stresses, except high osmotic stress. Notably, we find Ssk1 regulates Hog1 in a two-component independent manner by functioning to promote interactions between the Ssk2 and Pbs2 kinases. We propose this function of Ssk1 is important to maintain a basal level of Hog1 phosphorylation which is necessary for oxidative stress, but not osmotic stress, mediated Hog1 activation. We find that osmotic stress triggers robust Pbs2 phosphorylation which drives its dissociation from Ssk2. In contrast, Pbs2 is not robustly phosphorylated following oxidative stress and the Ssk1-mediated Ssk2-Pbs2 interaction remains intact. Instead, oxidative stress-stimulated increases in phosphorylated Hog1 is dependent on the inhibition of protein tyrosine phosphatases that negatively regulate Hog1 coupled with the Ssk1-mediated promotion of basal Hog1 activity. Furthermore, we find that inhibition of protein tyrosine phosphatases is linked to the hydrogen peroxide induced oxidation of these negative regulators in a mechanism that is partly dependent on thioredoxin. Taken together these data reveal stress contingent changes in Hog1 pathway architecture and regulation and uncover a novel mode of action of the Ssk1 response regulator in SAPK regulation.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1012314","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T13:48:23Z","timestamp":1734961703000},"page":"e1012314","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["Stress contingent changes in Hog1 pathway architecture and regulation in Candida albicans"],"prefix":"10.1371","volume":"20","author":[{"given":"Alison M.","family":"Day","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra da Silva","family":"Dantas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Ianieva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Herrero-de-Dios","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alistair J. P.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8732-7676","authenticated-orcid":true,"given":"Janet","family":"Quinn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,12,23]]},"reference":[{"issue":"4","key":"ppat.1012314.ref001","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/s41579-023-00861-x","article-title":"The WHO fungal priority pathogens list as a game-changer","volume":"21","author":"MC Fisher","year":"2023","journal-title":"Nat Rev Microbiol"},{"issue":"2","key":"ppat.1012314.ref002","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.chom.2017.07.002","article-title":"Commensal Fungi in Health and Disease","volume":"22","author":"JJ Limon","year":"2017","journal-title":"Cell Host Microbe"},{"issue":"8","key":"ppat.1012314.ref003","article-title":"Current Antimycotics, New Prospects, and Future Approaches to Antifungal Therapy.","volume":"9","author":"G Wall","year":"2020","journal-title":"Antibiotics (Basel)."},{"issue":"6","key":"ppat.1012314.ref004","doi-asserted-by":"crossref","first-page":"3390","DOI":"10.1021\/acs.chemrev.0c00199","article-title":"Antifungal Drug Resistance: Molecular Mechanisms in Candida albicans and Beyond","volume":"121","author":"Y Lee","year":"2021","journal-title":"Chem Rev"},{"issue":"10","key":"ppat.1012314.ref005","doi-asserted-by":"crossref","first-page":"1200","DOI":"10.1016\/j.cmi.2019.04.024","article-title":"Morbidity and mortality of candidaemia in Europe: an epidemiologic meta-analysis","volume":"25","author":"P Koehler","year":"2019","journal-title":"Clin Microbiol Infect"},{"issue":"9","key":"ppat.1012314.ref006","doi-asserted-by":"crossref","first-page":"e449","DOI":"10.1093\/cid\/ciaa193","article-title":"Burden of Candidemia in the United States, 2017","volume":"71","author":"SV Tsay","year":"2020","journal-title":"Clin Infect Dis"},{"issue":"4","key":"ppat.1012314.ref007","article-title":"Stress Adaptation.","volume":"5","author":"AJP Brown","year":"2017","journal-title":"Microbiology spectrum"},{"issue":"5","key":"ppat.1012314.ref008","doi-asserted-by":"crossref","first-page":"e1008478","DOI":"10.1371\/journal.ppat.1008478","article-title":"Adapting to survive: How Candida overcomes host-imposed constraints during human colonization.","volume":"16","author":"R Alves","year":"2020","journal-title":"PLoS pathogens"},{"key":"ppat.1012314.ref009","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1146\/annurev-immunol-020711-074942","article-title":"Neutrophil function: from mechanisms to disease","volume":"30","author":"B Amulic","year":"2012","journal-title":"Annu Rev Immunol"},{"issue":"5","key":"ppat.1012314.ref010","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1111\/j.1365-2958.2004.04350.x","article-title":"Transcriptional profiling in Candida albicans reveals new adaptive responses to extracellular pH and functions for Rim101p","volume":"54","author":"ES Bensen","year":"2004","journal-title":"Molecular microbiology"},{"issue":"1","key":"ppat.1012314.ref011","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1007\/s004240050371","article-title":"Solute composition and heat shock proteins in rat renal medulla","volume":"434","author":"A Ohno","year":"1997","journal-title":"Pflugers Arch"},{"issue":"10","key":"ppat.1012314.ref012","doi-asserted-by":"crossref","DOI":"10.1242\/dmm.050393","article-title":"How metals fuel fungal virulence, yet promote anti-fungal immunity","volume":"16","author":"A Alselami","year":"2023","journal-title":"Dis Model Mech"},{"key":"ppat.1012314.ref013","doi-asserted-by":"crossref","first-page":"261","DOI":"10.3389\/fcimb.2019.00261","article-title":"Stress-Activated Protein Kinases in Human Fungal Pathogens.","volume":"9","author":"AM Day","year":"2019","journal-title":"Front Cell Infect Microbiol"},{"issue":"10","key":"ppat.1012314.ref014","doi-asserted-by":"crossref","first-page":"3058","DOI":"10.1128\/JB.181.10.3058-3068.1999","article-title":"Role of the mitogen-activated protein kinase Hog1p in morphogenesis and virulence of Candida albicans","volume":"181","author":"R Alonso-Monge","year":"1999","journal-title":"Journal of bacteriology"},{"issue":"12","key":"ppat.1012314.ref015","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1128\/EC.00235-14","article-title":"A novel function for Hog1 stress-activated protein kinase in controlling white-opaque switching and mating in Candida albicans","volume":"13","author":"SH Liang","year":"2014","journal-title":"Eukaryotic cell"},{"issue":"Pt 2","key":"ppat.1012314.ref016","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1099\/mic.0.023309-0","article-title":"The Hog1 MAP kinase controls respiratory metabolism in the fungal pathogen Candida albicans","volume":"155","author":"R Alonso-Monge","year":"2009","journal-title":"Microbiology (Reading, England)."},{"issue":"4","key":"ppat.1012314.ref017","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.01581-18","article-title":"High-Throughput Screening Identifies Genes Required for Candida albicans Induction of Macrophage Pyroptosis.","volume":"9","author":"TR O\u2019Meara","year":"2018","journal-title":"mBio"},{"issue":"3","key":"ppat.1012314.ref018","doi-asserted-by":"crossref","first-page":"e1008052","DOI":"10.1371\/journal.pgen.1008052","article-title":"The p38\/HOG stress-activated protein kinase network couples growth to division in Candida albicans","volume":"15","author":"A Sellam","year":"2019","journal-title":"PLoS genetics"},{"issue":"49","key":"ppat.1012314.ref019","doi-asserted-by":"crossref","first-page":"42002","DOI":"10.1074\/jbc.M111.265231","article-title":"MAPKKK-independent regulation of the Hog1 stress-activated protein kinase in Candida albicans","volume":"286","author":"J Cheetham","year":"2011","journal-title":"The Journal of biological chemistry"},{"issue":"1","key":"ppat.1012314.ref020","doi-asserted-by":"crossref","first-page":"e87128","DOI":"10.1371\/journal.pone.0087128","article-title":"The HOG pathway is critical for the colonization of the mouse gastrointestinal tract by Candida albicans.","volume":"9","author":"D Prieto","year":"2014","journal-title":"PloS one"},{"issue":"7","key":"ppat.1012314.ref021","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1111\/j.1462-5822.2007.00898.x","article-title":"Differential susceptibility of mitogen-activated protein kinase pathway mutants to oxidative-mediated killing by phagocytes in the fungal pathogen Candida albicans","volume":"9","author":"DM Arana","year":"2007","journal-title":"Cellular microbiology"},{"issue":"2","key":"ppat.1012314.ref022","article-title":"Redox Regulation, Rather than Stress-Induced Phosphorylation, of a Hog1 Mitogen-Activated Protein Kinase Modulates Its Nitrosative-Stress-Specific Outputs.","volume":"9","author":"C Herrero-de-Dios","year":"2018","journal-title":"mBio"},{"key":"ppat.1012314.ref023","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/1471-2148-9-44","article-title":"Phylogenetic diversity of stress signalling pathways in fungi","volume":"9","author":"E Nikolaou","year":"2009","journal-title":"BMC evolutionary biology"},{"issue":"1","key":"ppat.1012314.ref024","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/sj.cr.7290257","article-title":"Activation and signaling of the p38 MAP kinase pathway","volume":"15","author":"T Zarubin","year":"2005","journal-title":"Cell Res"},{"issue":"Pt 4","key":"ppat.1012314.ref025","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1099\/mic.0.27723-0","article-title":"The Pbs2 MAP kinase kinase is essential for the oxidative-stress response in the fungal pathogen Candida albicans","volume":"151","author":"DM Arana","year":"2005","journal-title":"Microbiology (Reading, England)."},{"issue":"11","key":"ppat.1012314.ref026","doi-asserted-by":"crossref","first-page":"4603","DOI":"10.1091\/mbc.e07-06-0581","article-title":"A single MAPKKK regulates the Hog1 MAPK pathway in the pathogenic fungus Candida albicans","volume":"18","author":"J Cheetham","year":"2007","journal-title":"Molecular biology of the cell"},{"issue":"5319","key":"ppat.1012314.ref027","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1126\/science.276.5319.1702","article-title":"Osmotic activation of the HOG MAPK pathway via Ste11p MAPKKK: scaffold role of Pbs2p MAPKK","volume":"276","author":"F Posas","year":"1997","journal-title":"Science (New York, NY)."},{"issue":"3","key":"ppat.1012314.ref028","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1091\/mbc.e12-06-0477","article-title":"Reduced TOR signaling sustains hyphal development in Candida albicans by lowering Hog1 basal activity","volume":"24","author":"C Su","year":"2013","journal-title":"Molecular biology of the cell"},{"issue":"2","key":"ppat.1012314.ref029","doi-asserted-by":"crossref","first-page":"e1004632","DOI":"10.1371\/journal.ppat.1004632","article-title":"A case for two-component signaling systems as antifungal drug targets.","volume":"11","author":"E Shor","year":"2015","journal-title":"PLoS pathogens."},{"issue":"1","key":"ppat.1012314.ref030","doi-asserted-by":"crossref","first-page":"1884","DOI":"10.1080\/21505594.2021.1949883","article-title":"The two-component signal transduction system and its regulation in Candida albicans.","volume":"12","author":"B Liao","year":"2021","journal-title":"Virulence"},{"issue":"1","key":"ppat.1012314.ref031","doi-asserted-by":"crossref","first-page":"e1006131","DOI":"10.1371\/journal.ppat.1006131","article-title":"Blocking two-component signalling enhances Candida albicans virulence and reveals adaptive mechanisms that counteract sustained SAPK activation.","volume":"13","author":"AM Day","year":"2017","journal-title":"PLoS pathogens"},{"issue":"5","key":"ppat.1012314.ref032","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1093\/emboj\/17.5.1385","article-title":"Activation of the yeast SSK2 MAP kinase kinase kinase by the SSK1 two-component response regulator","volume":"17","author":"F Posas","year":"1998","journal-title":"The EMBO journal"},{"issue":"5","key":"ppat.1012314.ref033","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1128\/EC.2.5.1018-1024.2003","article-title":"Candida albicans response regulator gene SSK1 regulates a subset of genes whose functions are associated with cell wall biosynthesis and adaptation to oxidative stress","volume":"2","author":"N Chauhan","year":"2003","journal-title":"Eukaryotic cell"},{"issue":"23","key":"ppat.1012314.ref034","doi-asserted-by":"crossref","first-page":"10611","DOI":"10.1128\/MCB.25.23.10611-10627.2005","article-title":"The Sho1 adaptor protein links oxidative stress to morphogenesis and cell wall biosynthesis in the fungal pathogen Candida albicans","volume":"25","author":"E Roman","year":"2005","journal-title":"Molecular and cellular biology"},{"issue":"4","key":"ppat.1012314.ref035","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1111\/j.1365-2958.2006.05438.x","article-title":"Functional studies of the Ssk1p response regulator protein of Candida albicans as determined by phenotypic analysis of receiver domain point mutants","volume":"62","author":"V Menon","year":"2006","journal-title":"Molecular microbiology"},{"issue":"2","key":"ppat.1012314.ref036","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1128\/IAI.68.2.518-525.2000","article-title":"Defective hyphal development and avirulence caused by a deletion of the SSK1 response regulator gene in Candida albicans","volume":"68","author":"JA Calera","year":"2000","journal-title":"Infection and immunity"},{"key":"ppat.1012314.ref037","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/0076-6879(91)94004-V","article-title":"Getting started with yeast","volume":"194","author":"F. Sherman","year":"1991","journal-title":"Methods in enzymology"},{"issue":"12","key":"ppat.1012314.ref038","doi-asserted-by":"crossref","first-page":"e27979","DOI":"10.1371\/journal.pone.0027979","article-title":"Identification of a novel response regulator, Crr1, that is required for hydrogen peroxide resistance in Candida albicans.","volume":"6","author":"CR Bruce","year":"2011","journal-title":"PloS one"},{"issue":"4","key":"ppat.1012314.ref039","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1002\/1097-0061(20000315)16:4<325::AID-YEA538>3.0.CO;2-#","article-title":"CIp10, an efficient and convenient integrating vector for Candida albicans","volume":"16","author":"AM Murad","year":"2000","journal-title":"Yeast"},{"issue":"2","key":"ppat.1012314.ref040","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1128\/EC.4.2.298-309.2005","article-title":"Strains and strategies for large-scale gene deletion studies of the diploid human fungal pathogen Candida albicans","volume":"4","author":"SM Noble","year":"2005","journal-title":"Eukaryotic cell"},{"issue":"9","key":"ppat.1012314.ref041","first-page":"737","article-title":"Gene disruption in Candida albicans using a synthetic, codon-optimised Cre-loxP system. Fungal genetics and biology: FG &","volume":"42","author":"PM Dennison","year":"2005","journal-title":"B"},{"issue":"3","key":"ppat.1012314.ref042","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1093\/genetics\/134.3.717","article-title":"Isogenic strain construction and gene mapping in Candida albicans","volume":"134","author":"WA Fonzi","year":"1993","journal-title":"Genetics"},{"key":"ppat.1012314.ref043","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1186\/1471-2164-9-578","article-title":"A toolbox for epitope-tagging and genome-wide location analysis in Candida albicans","volume":"9","author":"H Lavoie","year":"2008","journal-title":"BMC Genomics"},{"issue":"9","key":"ppat.1012314.ref044","doi-asserted-by":"crossref","first-page":"4179","DOI":"10.1091\/mbc.e04-03-0181","article-title":"A conserved stress-activated protein kinase regulates a core stress response in the human pathogen Candida albicans","volume":"15","author":"DA Smith","year":"2004","journal-title":"Molecular biology of the cell"},{"issue":"2","key":"ppat.1012314.ref045","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1091\/mbc.e05-06-0501","article-title":"Role of the Hog1 stress-activated protein kinase in the global transcriptional response to stress in the fungal pathogen Candida albicans","volume":"17","author":"B Enjalbert","year":"2006","journal-title":"Molecular biology of the cell"},{"issue":"19","key":"ppat.1012314.ref046","doi-asserted-by":"crossref","first-page":"4550","DOI":"10.1128\/MCB.00313-10","article-title":"Thioredoxin regulates multiple hydrogen peroxide-induced signaling pathways in Candida albicans","volume":"30","author":"A da Silva Dantas","year":"2010","journal-title":"Molecular and cellular biology"},{"issue":"18","key":"ppat.1012314.ref047","doi-asserted-by":"crossref","first-page":"6662","DOI":"10.1128\/MCB.23.18.6662-6671.2003","article-title":"Phosphorelay-regulated degradation of the yeast Ssk1p response regulator by the ubiquitin-proteasome system","volume":"23","author":"N Sato","year":"2003","journal-title":"Molecular and cellular biology"},{"issue":"2","key":"ppat.1012314.ref048","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1091\/mbc.e03-07-0521","article-title":"Unique and redundant roles for HOG MAPK pathway components as revealed by whole-genome expression analysis","volume":"15","author":"SM O\u2019Rourke","year":"2004","journal-title":"Molecular biology of the cell"},{"issue":"15","key":"ppat.1012314.ref049","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.1091\/mbc.E18-03-0185","article-title":"Intracellular mechanism by which arsenite activates the yeast stress MAPK Hog1","volume":"29","author":"J Lee","year":"2018","journal-title":"Molecular biology of the cell"},{"issue":"13","key":"ppat.1012314.ref050","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1101\/gad.13.13.1653","article-title":"Heat-shock-induced activation of stress MAP kinase is regulated by threonine- and tyrosine-specific phosphatases","volume":"13","author":"AN Nguyen","year":"1999","journal-title":"Genes & development"},{"issue":"17","key":"ppat.1012314.ref051","doi-asserted-by":"crossref","first-page":"3140","DOI":"10.1016\/j.molcel.2023.07.018","article-title":"A peroxiredoxin-P38 MAPK scaffold increases MAPK activity by MAP3K-independent mechanisms","volume":"83","author":"M Cao","year":"2023","journal-title":"Molecular cell"},{"issue":"5223","key":"ppat.1012314.ref052","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1126\/science.7624781","article-title":"Activation of yeast PBS2 MAPKK by MAPKKKs or by binding of an SH3-containing osmosensor","volume":"269","author":"T Maeda","year":"1995","journal-title":"Science (New York, NY)."},{"issue":"6","key":"ppat.1012314.ref053","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/S0092-8674(00)80162-2","article-title":"Yeast HOG1 MAP kinase cascade is regulated by a multistep phosphorelay mechanism in the SLN1-YPD1-SSK1 \"two-component\" osmosensor.","volume":"86","author":"F Posas","year":"1996","journal-title":"Cell"},{"issue":"2","key":"ppat.1012314.ref054","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1091\/mbc.12.2.407","article-title":"Peroxide sensors for the fission yeast stress-activated mitogen-activated protein kinase pathway","volume":"12","author":"V Buck","year":"2001","journal-title":"Molecular biology of the cell"},{"issue":"8","key":"ppat.1012314.ref055","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1101\/gad.11.8.1008","article-title":"The Mcs4 response regulator coordinately controls the stress-activated Wak1-Wis1-Sty1 MAP kinase pathway and fission yeast cell cycle","volume":"11","author":"JC Shieh","year":"1997","journal-title":"Genes & development"},{"issue":"7","key":"ppat.1012314.ref056","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1091\/mbc.e12-10-0727","article-title":"Response regulator-mediated MAPKKK heteromer promotes stress signaling to the Spc1 MAPK in fission yeast","volume":"24","author":"S Morigasaki","year":"2013","journal-title":"Molecular biology of the cell"},{"issue":"7","key":"ppat.1012314.ref057","doi-asserted-by":"crossref","first-page":"3122","DOI":"10.1091\/mbc.e06-02-0113","article-title":"A unique fungal two-component system regulates stress responses, drug sensitivity, sexual development, and virulence of Cryptococcus neoformans","volume":"17","author":"YS Bahn","year":"2006","journal-title":"Molecular biology of the cell"},{"issue":"5","key":"ppat.1012314.ref058","doi-asserted-by":"crossref","DOI":"10.1128\/mSphere.00973-20","article-title":"The Two-Component Response Regulator Ssk1 and the Mitogen-Activated Protein Kinase Hog1 Control Antifungal Drug Resistance and Cell Wall Architecture of Candida auris.","volume":"5","author":"R Shivarathri","year":"2020","journal-title":"mSphere"},{"issue":"2","key":"ppat.1012314.ref059","doi-asserted-by":"crossref","first-page":"e0149153","DOI":"10.1371\/journal.pone.0149153","article-title":"How the Pathogenic Fungus Alternaria alternata Copes with Stress via the Response Regulators SSK1 and SHO1.","volume":"11","author":"PL Yu","year":"2016","journal-title":"PloS one"},{"issue":"12","key":"ppat.1012314.ref060","doi-asserted-by":"crossref","first-page":"1867","DOI":"10.1128\/EC.00150-10","article-title":"Histidine kinase two-component response regulator proteins regulate reproductive development, virulence, and stress responses of the fungal cereal pathogens Cochliobolus heterostrophus and Gibberella zeae","volume":"9","author":"S Oide","year":"2010","journal-title":"Eukaryotic cell"},{"issue":"3","key":"ppat.1012314.ref061","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1083\/jcb.118.3.561","article-title":"Osmotic stress and the yeast cytoskeleton: phenotype-specific suppression of an actin mutation","volume":"118","author":"S Chowdhury","year":"1992","journal-title":"J Cell Biol"},{"issue":"7","key":"ppat.1012314.ref062","doi-asserted-by":"crossref","first-page":"3013","DOI":"10.1091\/mbc.e02-11-0747","article-title":"Actin recovery and bud emergence in osmotically stressed cells requires the conserved actin interacting mitogen-activated protein kinase kinase kinase Ssk2p\/MTK1 and the scaffold protein Spa2p","volume":"14","author":"T Yuzyuk","year":"2003","journal-title":"Molecular biology of the cell"},{"issue":"8","key":"ppat.1012314.ref063","doi-asserted-by":"crossref","first-page":"2869","DOI":"10.1091\/mbc.02-01-0004","article-title":"The MEK kinase Ssk2p promotes actin cytoskeleton recovery after osmotic stress","volume":"13","author":"T Yuzyuk","year":"2002","journal-title":"Molecular biology of the cell"},{"issue":"5","key":"ppat.1012314.ref064","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.cell.2005.05.016","article-title":"Redox redux: revisiting PTPs and the control of cell signaling","volume":"121","author":"NK Tonks","year":"2005","journal-title":"Cell"},{"issue":"Pt 2","key":"ppat.1012314.ref065","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1099\/00221287-143-2-297","article-title":"Cloning, analysis and one-step disruption of the ARG5,6 gene of Candida albicans","volume":"143","author":"A Negredo","year":"1997","journal-title":"Microbiology (Reading)."}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1012314","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1012314","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T13:51:04Z","timestamp":1736257864000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1012314"}},"subtitle":[],"editor":[{"given":"Brian M.","family":"Peters","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,12,23]]},"references-count":65,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2024,12,23]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1012314","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,23]]}}}