{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T20:05:56Z","timestamp":1784837156520,"version":"3.55.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1014424","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000}}],"reference-count":34,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010438","name":"Francis Crick Institute","doi-asserted-by":"publisher","award":["CC2075"],"award-info":[{"award-number":["CC2075"]}],"id":[{"id":"10.13039\/100010438","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/R011834\/1"],"award-info":[{"award-number":["BB\/R011834\/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\/V031058\/1"],"award-info":[{"award-number":["MR\/V031058\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["EP\/X02377X\/1"],"award-info":[{"award-number":["EP\/X02377X\/1"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Research council"},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["222528\/Z\/21\/Z"],"award-info":[{"award-number":["222528\/Z\/21\/Z"]}],"id":[{"id":"10.13039\/100010269","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 pathogen\n                    <jats:italic>Salmonella<\/jats:italic>\n                    , which causes significant human morbidity and mortality, encodes an effector kinase, SteC, which mediates actin polymerisation and cell migration. Given the minimal nature of its kinase domain, it remains unclear how SteC is catalytically active and how this activity is regulated. Here, we show that SteC is activated following the phosphorylation of the highly conserved S379 residue,\u00a0which can be carried out by a host kinase. Phosphorylation of S379 dramatically increases nucleotide binding affinity of SteC, enabling substrate phosphorylation and promoting actin polymerisation. Further mutational analysis identified the functional role of HD and DGD motifs that likely mimic the HxD and DFG motifs of eukaryotic kinases. Meanwhile, the C-tail of SteC, encompassing amino acids 429\u2013457, is essential for function following translocation from\n                    <jats:italic>Salmonella<\/jats:italic>\n                    , but dispensable for catalysis\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Overall, our findings uncover two previously unappreciated mechanisms that mediate the activity of the only\n                    <jats:italic>Salmonella<\/jats:italic>\n                    effector kinase within the host.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014424","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T17:45:52Z","timestamp":1784223952000},"page":"e1014424","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Salmonella effector kinase SteC is activated by phosphorylation at Serine 379"],"prefix":"10.1371","volume":"22","author":[{"given":"Timesh D.","family":"Pillay","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Briac","family":"Lemetais","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Huber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ines","family":"Diaz del Olmo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Masino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Maslen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Esposito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay C. D.","family":"Hinton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiujun","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa L. M.","family":"Thurston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7698-4435","authenticated-orcid":true,"given":"Katrin","family":"Rittinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"key":"ppat.1014424.ref001","doi-asserted-by":"crossref","first-page":"941","DOI":"10.3201\/eid2106.140999","article-title":"Global burden of invasive nontyphoidal salmonella disease, 2010","volume":"21","author":"TT Ao","year":"2015","journal-title":"Emerg Infect Dis"},{"key":"ppat.1014424.ref002","unstructured":"Global Burden of Disease Collaborators. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017. Preprint. 2018."},{"issue":"12","key":"ppat.1014424.ref003","doi-asserted-by":"crossref","first-page":"1312","DOI":"10.1016\/S1473-3099(19)30418-9","article-title":"The global burden of non-typhoidal salmonella invasive disease: a systematic analysis for the Global Burden of Disease Study 2017","volume":"19","author":"Collaborators GBD 2017 Non-Typhoidal Salmonella Invasive Disease","year":"2019","journal-title":"Lancet Infect Dis"},{"issue":"6","key":"ppat.1014424.ref004","doi-asserted-by":"crossref","first-page":"001342","DOI":"10.1099\/mic.0.001342","article-title":"Speaking the host language: how Salmonella effector proteins manipulate the host","volume":"169","author":"TD Pillay","year":"2023","journal-title":"Microbiology (Reading)"},{"issue":"5","key":"ppat.1014424.ref005","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.chom.2012.09.011","article-title":"The Salmonella kinase SteC targets the MAP kinase MEK to regulate the host actin cytoskeleton","volume":"12","author":"C Odendall","year":"2012","journal-title":"Cell Host Microbe"},{"issue":"22","key":"ppat.1014424.ref006","doi-asserted-by":"crossref","first-page":"4430","DOI":"10.1091\/mbc.e12-03-0243","article-title":"The Salmonella Typhimurium effector SteC inhibits Cdc42-mediated signaling through binding to the exchange factor Cdc24 in Saccharomyces cerevisiae","volume":"23","author":"P Fernandez-Pi\u00f1ar","year":"2012","journal-title":"Mol Biol Cell"},{"issue":"8","key":"ppat.1014424.ref007","doi-asserted-by":"crossref","DOI":"10.1016\/j.chom.2021.06.004","article-title":"Global mapping of Salmonella enterica-host protein-protein interactions during infection","volume":"29","author":"P Walch","year":"2021","journal-title":"Cell Host Microbe"},{"issue":"8","key":"ppat.1014424.ref008","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1038\/s44318-024-00076-7","article-title":"Salmonella manipulates macrophage migration via SteC-mediated myosin light chain activation to penetrate the gut-vascular barrier","volume":"43","author":"Y Dai","year":"2024","journal-title":"EMBO J"},{"issue":"1","key":"ppat.1014424.ref009","first-page":"20","article-title":"SteC is a Salmonella kinase required for SPI-2-dependent F-actin remodelling","volume":"10","author":"J Poh","year":"2008","journal-title":"Cell Microbiol"},{"issue":"8","key":"ppat.1014424.ref010","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1096\/fasebj.9.8.7768349","article-title":"The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification 1","volume":"9","author":"SK Hanks","year":"1995","journal-title":"The FASEB Journal"},{"issue":"1","key":"ppat.1014424.ref011","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1002\/chem.201503552","article-title":"Addressing the Glycine-Rich Loop of Protein Kinases by a Multi-Facetted Interaction Network: Inhibition of PKA and a PKB Mimic","volume":"22","author":"BS Lauber","year":"2016","journal-title":"Chemistry"},{"key":"ppat.1014424.ref012","doi-asserted-by":"crossref","unstructured":"Carrera AC, Alexandrov K, Roberts TM. 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