{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:53:50Z","timestamp":1792788830726,"version":"4.5.0"},"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Guangdong Basic and Applied Basic Research Foundation","award":["2025A1515012727"],"award-info":[{"award-number":["2025A1515012727"]}]},{"name":"National key research and development program of China","award":["2024YFD2401803"],"award-info":[{"award-number":["2024YFD2401803"]}]},{"name":"Postgraduate Education Innovation Project of Guangdong Ocean University","award":["202555"],"award-info":[{"award-number":["202555"]}],"id":[{"id":"https:\/\/ror.org\/0462wa640","id-type":"ROR","asserted-by":"crossref"}]},{"name":"the Projects of Innovation Team of Colleges and Universities in Guangdong Province","award":["2022KCXTD013"],"award-info":[{"award-number":["2022KCXTD013"]}]},{"name":"2025 basic ability improvement project for young and middle-aged teachers in colleges and universities in Guangxi","award":["2025KY2107; 2025KY2110"],"award-info":[{"award-number":["2025KY2107; 2025KY2110"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    <jats:italic>MKK6<\/jats:italic>\n                    is a key protein kinase that regulates inflammatory response under pathogen infection by activating MAPK signal pathway. However, the function of\n                    <jats:italic>MKK6<\/jats:italic>\n                    remained unclear within oysters. Our research recognized a novel\n                    <jats:italic>KK6<\/jats:italic>\n                    gene from\n                    <jats:italic>C. hongkongensis<\/jats:italic>\n                    , which is named\n                    <jats:italic>ChMKK6<\/jats:italic>\n                    . The cDNA of\n                    <jats:italic>ChMKK6<\/jats:italic>\n                    gene was 2,760 bp in length, containing an ORF of 1,032 bp encoding 344 amino acids, with a conserved S-TKc region and a DVD region. As illustrated by amino acid alignment and phylogenetic tree,\n                    <jats:italic>ChMKK6<\/jats:italic>\n                    shared the maximal (99.0%) identity showing\n                    <jats:italic>MKK6<\/jats:italic>\n                    of\n                    <jats:italic>Crassostrea gigas.<\/jats:italic>\n                    As indicated by tissue expression analysis,\n                    <jats:italic>ChMKK6<\/jats:italic>\n                    possessed the maximal expression within hepatopancreas, and was markedly increased in all tissues following\n                    <jats:italic>Vibrio Parahaemolyticus<\/jats:italic>\n                    (\n                    <jats:italic>V. Parahaemolyticus<\/jats:italic>\n                    ) challenge. As stated by the qRT-PCR analysis,\n                    <jats:italic>ChMKK6<\/jats:italic>\n                    silencing significantly suppressed\n                    <jats:italic>IL17<\/jats:italic>\n                    transcription, suggesting its involvement in innate immunity by regulating\n                    <jats:italic>IL17<\/jats:italic>\n                    -mediated inflammatory response. Moreover,\n                    <jats:italic>ChMKK6<\/jats:italic>\n                    silencing led to the suppression of key immune-related enzyme activities (ACP, AKP, CAT, LZM, and SOD), while raising the MDA content in gill. In addition, the antimicrobial viability of hemolymph supernatant was markedly reduced by\n                    <jats:italic>ChMKK6<\/jats:italic>\n                    silencing. These results collectively demonstrate that\n                    <jats:italic>ChMKK6<\/jats:italic>\n                    is a key player in immunity defense of\n                    <jats:italic>C. hongkongensis<\/jats:italic>\n                    from\n                    <jats:italic>V. Parahaemolyticus.<\/jats:italic>\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0360613","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:23:52Z","timestamp":1792085032000},"page":"e0360613","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Recognition and function analysis of MKK6 in immune reaction against Vibrio Parahaemolyticus in Crassostrea hongkongensis"],"prefix":"10.1371","volume":"21","author":[{"given":"Jiexiong","family":"Zhu","sequence":"first","affiliation":[{"name":"Fishery College of Guangdong Ocean University","place":["Zhanjiang, China"]},{"name":"Academician Joint Laboratory of Germplasm Resource Exploitation, Utilization and Health Assessment for Aquatic Animal, Guangdong Ocean University","place":["Zhanjiang, China"]},{"name":"Guangdong Provincial Key Laboratory of Aquatic Animal Disease Control and Healthy Culture, College of Fisheries, Guangdong Ocean University","place":["Zhanjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohui","family":"Shao","sequence":"additional","affiliation":[{"name":"Fishery College of Guangdong Ocean University","place":["Zhanjiang, China"]},{"name":"Academician Joint Laboratory of Germplasm Resource Exploitation, Utilization and Health Assessment for Aquatic Animal, Guangdong Ocean University","place":["Zhanjiang, China"]},{"name":"Guangdong Provincial Key Laboratory of Aquatic Animal Disease Control and Healthy Culture, College of Fisheries, Guangdong Ocean University","place":["Zhanjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Chen","sequence":"additional","affiliation":[{"name":"Vocational and Technical College","place":["Fangchenggang, Fangchenggang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinji","family":"Lin","sequence":"additional","affiliation":[{"name":"Vocational and Technical College","place":["Fangchenggang, Fangchenggang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiwen","family":"Liang","sequence":"additional","affiliation":[{"name":"Fishery College of Guangdong Ocean University","place":["Zhanjiang, China"]},{"name":"Academician Joint Laboratory of Germplasm Resource Exploitation, Utilization and Health Assessment for Aquatic Animal, Guangdong Ocean University","place":["Zhanjiang, China"]},{"name":"Guangdong Provincial Key Laboratory of Aquatic Animal Disease Control and Healthy Culture, College of Fisheries, Guangdong Ocean University","place":["Zhanjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7526-249X","authenticated-orcid":true,"given":"Feifei","family":"Yu","sequence":"additional","affiliation":[{"name":"Fishery College of Guangdong Ocean University","place":["Zhanjiang, China"]},{"name":"Academician Joint Laboratory of Germplasm Resource Exploitation, Utilization and Health Assessment for Aquatic Animal, Guangdong Ocean University","place":["Zhanjiang, China"]},{"name":"Guangdong Provincial Key Laboratory of Aquatic Animal Disease Control and Healthy Culture, College of Fisheries, Guangdong Ocean University","place":["Zhanjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiwen","family":"Wang","sequence":"additional","affiliation":[{"name":"Fishery College of Guangdong Ocean University","place":["Zhanjiang, China"]},{"name":"Academician Joint Laboratory of Germplasm Resource Exploitation, Utilization and Health Assessment for Aquatic Animal, Guangdong Ocean University","place":["Zhanjiang, China"]},{"name":"Guangdong Provincial Key Laboratory of Aquatic Animal Disease Control and Healthy Culture, College of Fisheries, Guangdong Ocean University","place":["Zhanjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baixu","family":"Lin","sequence":"additional","affiliation":[{"name":"Fishery College of Guangdong Ocean University","place":["Zhanjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongyao","family":"Huang","sequence":"additional","affiliation":[{"name":"Fishery College of Guangdong Ocean University","place":["Zhanjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyan","family":"Li","sequence":"additional","affiliation":[{"name":"Fishery College of Guangdong Ocean University","place":["Zhanjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhui","family":"Xu","sequence":"additional","affiliation":[{"name":"Fishery College of Guangdong Ocean University","place":["Zhanjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,10,15]]},"reference":[{"key":"pone.0360613.ref001","doi-asserted-by":"crossref","first-page":"110474","DOI":"10.1016\/j.fsi.2025.110474","article-title":"Genome-wide identification of ApeC domain-containing protein and revealing the function of ChACP-1.10 in oyster mucosal immunity","volume":"165","author":"T Lin","year":"2025","journal-title":"Fish Shellfish Immunol"},{"issue":"3","key":"pone.0360613.ref002","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1007\/s00248-018-1242-9","article-title":"Simulated marine heat wave alters abundance and structure of vibrio populations associated with the pacific oyster resulting in a mass mortality event","volume":"77","author":"TJ Green","year":"2018","journal-title":"Microb Ecol"},{"issue":"1","key":"pone.0360613.ref003","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.fsi.2013.11.008","article-title":"The protein expression profile in hepatopancreas of scallop Chlamys farreri under heat stress and Vibrio anguillarum challenge","volume":"36","author":"Z Sun","year":"2014","journal-title":"Fish Shellfish Immunol"},{"key":"pone.0360613.ref004","article-title":"Analysis of antimicrobial resistance and virulence of Vibrio parahaemolyticus","volume":"222","author":"ZQ Shen","year":"2026","journal-title":"Mar Pollut Bull"},{"issue":"3","key":"pone.0360613.ref005","article-title":"Vibrio spp. from Yesso scallop (Patinopecten yessoensis) demonstrating virulence properties and antimicrobial resistance","volume":"39","author":"BCJ De Silva","year":"2019","journal-title":"Journal of Food Safety"},{"key":"pone.0360613.ref006","article-title":"Transcriptome analysis reveals the function of TLR4-MyD88 pathway in immune response of Crassostrea hongkongensis against Vibrio parahaemolyticus","volume":"25","author":"J Chen","year":"2022","journal-title":"Aquac Rep"},{"key":"pone.0360613.ref007","doi-asserted-by":"crossref","first-page":"106695","DOI":"10.1016\/j.marenvres.2024.106695","article-title":"Characterization of MKK family genes and their responses to temperature stress and Vibrio parahaemolyticus infection in noble scallop Chlamys nobilis","volume":"201","author":"Y Zeng","year":"2024","journal-title":"Mar Environ Res"},{"issue":"6844","key":"pone.0360613.ref008","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1038\/35085597","article-title":"TAK1 is a ubiquitin-dependent kinase of MKK and IKK","volume":"412","author":"W Chen","year":"2001","journal-title":"Nature"},{"key":"pone.0360613.ref009","first-page":"119","article-title":"Cell type-specific signaling in response to interferon-\u03b3","volume":"316","author":"A van Boxel-Dezaire","year":"2007","journal-title":"Curr Top Microbiol Immunol"},{"key":"pone.0360613.ref010","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.molimm.2015.12.011","article-title":"MKK6 from pacific white shrimp Litopenaeus vannamei is responsive to bacterial and WSSV infection","volume":"70","author":"H Li","year":"2016","journal-title":"Mol Immunol"},{"key":"pone.0360613.ref011","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/j.fsi.2019.06.043","article-title":"A novel MKK gene (EcMKK6) in Epinephelus coioides: Identification, characterization and its response to Vibrio alginolyticus and SGIV infection","volume":"92","author":"YL Su","year":"2019","journal-title":"Fish Shellfish Immunol"},{"key":"pone.0360613.ref012","doi-asserted-by":"crossref","first-page":"554","DOI":"10.1016\/j.fsi.2019.12.080","article-title":"AP-1 regulates the expression of IL17-4 and IL17-5 in the pacific oyster Crassostrea gigas","volume":"97","author":"L Wang","year":"2020","journal-title":"Fish Shellfish Immunol"},{"key":"pone.0360613.ref013","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.fsi.2020.01.002","article-title":"Positive and negative regulatory effects of transcription factor activator protein 1 (AP1) on the expression of antimicrobial peptides in Macrobrachium nipponense","volume":"98","author":"C Zhang","year":"2020","journal-title":"Fish Shellfish Immunol"},{"issue":"1","key":"pone.0360613.ref014","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.fsi.2013.10.005","article-title":"Activator protein-1 (AP-1) and response to pathogen infection in the Hong Kong oyster (Crassostrea hongkongensis)","volume":"36","author":"Z Xiang","year":"2014","journal-title":"Fish Shellfish Immunol"},{"key":"pone.0360613.ref015","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.fsi.2019.08.013","article-title":"Insight into the molecular function and transcriptional regulation of activator protein 1 (AP-1) components c-Jun\/c-Fos ortholog in red lip mullet (Liza haematocheila)","volume":"93","author":"ND Janson","year":"2019","journal-title":"Fish Shellfish Immunol"},{"issue":"5","key":"pone.0360613.ref016","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1111\/j.1365-2672.1994.tb04403.x","article-title":"Partial purification and biochemical properties of acid and alkaline phosphatases from Myxococcus coralloides D","volume":"77","author":"F Gonz\u00e1lez","year":"1994","journal-title":"J Appl Bacteriol"},{"key":"pone.0360613.ref017","doi-asserted-by":"crossref","first-page":"626493","DOI":"10.3389\/fimmu.2021.626493","article-title":"Mitf involved in innate immunity by activating tyrosinase-mediated melanin synthesis in Pteria penguin","volume":"12","author":"F Yu","year":"2021","journal-title":"Front Immunol"},{"issue":"3","key":"pone.0360613.ref018","doi-asserted-by":"crossref","first-page":"100271","DOI":"10.1016\/j.watbs.2024.100271","article-title":"Chinese wisdom and modern innovation of aquaculture","volume":"3","author":"JF Gui","year":"2024","journal-title":"Water Biol Secur"},{"issue":"3","key":"pone.0360613.ref019","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1534\/g3.115.025650","article-title":"Aberrant activation of p38 MAP kinase-dependent innate immune responses is toxic to Caenorhabditis elegans","volume":"6","author":"HK Cheesman","year":"2016","journal-title":"G3: Genes Genomes Genet"},{"key":"pone.0360613.ref020","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/j.fsi.2018.10.073","article-title":"Mitogen-activated protein kinase kinase 6 is involved in the immune response to bacterial di-\/tripeptide challenge in grass carp Ctenopharyngodon idella","volume":"84","author":"F Qu","year":"2019","journal-title":"Fish Shellfish Immunol"},{"issue":"5","key":"pone.0360613.ref021","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1093\/jb\/mvs023","article-title":"Crystal structure of non-phosphorylated MAP2K6 in a putative auto-inhibition state","volume":"151","author":"T Matsumoto","year":"2012","journal-title":"J Biochem"},{"issue":"3","key":"pone.0360613.ref022","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1128\/MCB.16.3.1247","article-title":"MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway","volume":"16","author":"J Jo\u00eb","year":"1996","journal-title":"Mol Cell Biol"},{"issue":"3","key":"pone.0360613.ref023","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.cyto.2009.08.002","article-title":"Regulation of JNK and p38 MAPK in the immune system: Signal integration, propagation and termination","volume":"48","author":"G Huang","year":"2009","journal-title":"Cytokine"},{"key":"pone.0360613.ref024","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.fsi.2022.07.035","article-title":"NF-\u03baB-coupled IL17 mediates inflammatory signaling and intestinal inflammation in Artemia sinica","volume":"128","author":"Z Wang","year":"2022","journal-title":"Fish Shellfish Immunol"},{"key":"pone.0360613.ref025","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.fsi.2016.03.027","article-title":"Cloning and analysis of gene expression of interleukin-17 homolog in triangle-shell pearl mussel, Hyriopsis cumingii, during pearl sac formation","volume":"52","author":"R Zhang","year":"2016","journal-title":"Fish Shellfish Immunol"},{"issue":"6","key":"pone.0360613.ref026","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1111\/j.1462-2920.2005.00792.x","article-title":"Persistence of vibrios in marine bivalves: The role of interactions with haemolymph components","volume":"7","author":"C Pruzzo","year":"2005","journal-title":"Environ Microbiol"},{"key":"pone.0360613.ref027","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s12967-016-0833-9","article-title":"IL-17 mediates inflammatory reactions via p38\/c-Fos and JNK\/c-Jun activation in an AP-1-dependent manner in human nucleus pulposus cells","volume":"14","author":"JK Li","year":"2016","journal-title":"J Transl Med"},{"key":"pone.0360613.ref028","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.fsi.2017.08.018","article-title":"The expression of superoxide dismutase in Mytilus coruscus under various stressors","volume":"70","author":"J Wu","year":"2017","journal-title":"Fish Shellfish Immunol"},{"issue":"11","key":"pone.0360613.ref029","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1089\/ars.2011.4414","article-title":"Upsides and downsides of reactive oxygen species for cancer: The roles of reactive oxygen species in tumorigenesis, prevention, and therapy","volume":"16","author":"SC Gupta","year":"2012","journal-title":"Antioxid Redox Signal"},{"issue":"7","key":"pone.0360613.ref030","doi-asserted-by":"crossref","first-page":"3167","DOI":"10.7150\/thno.52028","article-title":"Holo-lactoferrin: The link between ferroptosis and radiotherapy in triple-negative breast cancer","volume":"11","author":"Z Zhang","year":"2021","journal-title":"Theranostics"},{"issue":"11","key":"pone.0360613.ref031","doi-asserted-by":"crossref","DOI":"10.1002\/slct.202103627","article-title":"Comparison of colorimetric methods to detect malondialdehyde, a biomarker of reactive oxygen species","volume":"7","author":"D Islayem","year":"2022","journal-title":"ChemistrySelect"},{"key":"pone.0360613.ref032","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.fsi.2019.12.094","article-title":"Non-specific immune factors differences in coelomic fluid from polian vesicle and coelom of Apostichopus japonicus, and their early response after evisceration","volume":"98","author":"Y Ren","year":"2020","journal-title":"Fish Shellfish Immunol"},{"issue":"2","key":"pone.0360613.ref033","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.jip.2010.11.007","article-title":"Comparison of antibacterial activity in the hemolymph of marine bivalves from Galicia (NW Spain)","volume":"106","author":"SM Casas","year":"2011","journal-title":"J Invertebr Pathol"},{"key":"pone.0360613.ref034","doi-asserted-by":"crossref","first-page":"108809","DOI":"10.1016\/j.fsi.2023.108809","article-title":"Creb2 involved in innate immunity by activating PpMitf-mediated melanogenesis in Pteria penguin","volume":"138","author":"F Yu","year":"2023","journal-title":"Fish Shellfish Immunol"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0360613","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:23:59Z","timestamp":1792085039000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0360613"}},"subtitle":[],"editor":[{"given":"Satheesh","family":"Sathianeson","sequence":"first","affiliation":[{"name":"King Abdulaziz University","place":["SAUDI ARABIA"]}],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,10,15]]},"references-count":34,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,10,15]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0360613","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,15]]}}}