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Previously, fludioxonil resistance was primarily associated with mutations in the histidine kinase Os1. However, highly resistant isolates without such mutations suggest the existence of additional mechanisms. This study identified a novel resistance pathway centered on the TGY motif of the terminal MAPK FgHog1 in Fusarium graminearum. Site-directed substitutions of phosphorylatable threonine and tyrosine residues in the TGY motif generated mutants FgHog1-T171G, FgHog1-Y173A, and double mutant FgHog1-T171G&amp;Y173A. All these mutations abolished detectable FgHog1 phosphorylation and conferred extremely high fludioxonil resistance. Loss of FgHog1 phosphorylation also blocked fludioxonil-induced nuclear translocation of FgHog1. However, nonphosphorylatable mutants exhibited severe defects in vegetative growth, sporulation, virulence, glycerol accumulation, acetic acid utilization, and sexual development, demonstrating strong pleiotropy. These results indicate that FgHog1 phosphorylation governs fludioxonil sensitivity and multiple biological functions, while the associated fitness costs may limit resistance development in field populations.<\/jats:p>","DOI":"10.1021\/acs.jafc.6c08357","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T11:50:07Z","timestamp":1788263407000},"page":"27475-27486","source":"Crossref","is-referenced-by-count":0,"title":["The Phosphorylation\nin TGY Motif of the Mitogen-Activated\nProtein Kinase Hog1 Governs Fludioxonil Resistance and Biological\nCharacteristics via Its Subcellular Localization in Filamentous Fungi"],"prefix":"10.1021","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-7544-0176","authenticated-orcid":true,"given":"Yinkai","family":"Liu","sequence":"first","affiliation":[{"name":"Nanjing Agricultural University , , , ,","place":["Nanjing, Jiangsu, China, 210095"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingchun","family":"Lv","sequence":"additional","affiliation":[{"name":"Nanjing Agricultural University , , , ,","place":["Nanjing, Jiangsu, China, 210095"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Wang","sequence":"additional","affiliation":[{"name":"Nanjing Agricultural University , , , ,","place":["Nanjing, Jiangsu, China, 210095"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolei","family":"Yang","sequence":"additional","affiliation":[{"name":"Nanjing Agricultural University , , , ,","place":["Nanjing, Jiangsu, China, 210095"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8520-4298","authenticated-orcid":true,"given":"Yige","family":"Li","sequence":"additional","affiliation":[{"name":"Nanjing Agricultural University , , , ,","place":["Nanjing, Jiangsu, China, 210095"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengxue","family":"Li","sequence":"additional","affiliation":[{"name":"Nanjing Agricultural University , , , ,","place":["Nanjing, Jiangsu, China, 210095"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiqiang","family":"Cai","sequence":"additional","affiliation":[{"name":"Nanjing Agricultural University , , , ,","place":["Nanjing, Jiangsu, China, 210095"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6085-9245","authenticated-orcid":true,"given":"Jun","family":"Yang","sequence":"additional","affiliation":[{"name":"China Agricultural University , , ,","place":["Beijing, China, 100193"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4183-8729","authenticated-orcid":true,"given":"Yabing","family":"Duan","sequence":"additional","affiliation":[{"name":"Nanjing Agricultural University , , , ,","place":["Nanjing, Jiangsu, China, 210095"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"issue":"2","key":"2026090917080000900_cit1","article-title":"The current status of wheat scab epidemic and chemical control and\ntheoretical innovation and application of key technologies for disease\ncontrol and mycotoxin reduction in China [in Chinese]","volume":"23","author":"Duan","year":"2024","journal-title":"Mod. 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