title: IKKβ phosphorylation regulates RPS3 nuclear translocation and NF-κB function during infection with Escherichia coli strain O157:H7.
abstract: NF-κB is a major gene regulator in immune responses, and ribosomal protein S3 (RPS3) is an NF-κB subunit that directs specific gene transcription. However, it is unknown how nuclear translocation of RPS3 is regulated. Here we report that phosphorylation of RPS3 Ser209 by the kinase IKKβ was crucial for nuclear localization of RPS3 in response to activating stimuli. Moreover, virulence protein NleH1 of the foodborne pathogen Escherichia coli strain O157:H7 specifically inhibited phosphorylation of RPS3 Ser209 and blocked RPS3 function, thereby promoting bacterial colonization and diarrhea but resulting in less mortality in a gnotobiotic piglet-infection model. Thus, the IKKβ-dependent modification of a specific amino acid in RPS3 promoted specific NF-κB functions that underlie the molecular pathogenetic mechanisms of E. coli O157:H7.
authors.affiliation: Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Fengyi
authors.initials: F
authors.lastname: Wan
authors.forename: Amanda
authors.initials: A
authors.lastname: Weaver
authors.forename: Xiaofei
authors.initials: X
authors.lastname: Gao
authors.forename: Michael
authors.initials: M
authors.lastname: Bern
authors.forename: Philip R
authors.initials: PR
authors.lastname: Hardwidge
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lenardo
mesh_terms: D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D004927:Escherichia coli Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology; D019453:Escherichia coli O157 / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism*; D015151:Immunoblotting; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D034622:RNA Interference; D012269:Ribosomal Proteins / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000235:genetics / Q000378:metabolism; D013552:Swine
chemical_list: D029968:Escherichia coli Proteins; D016328:NF-kappa B; C556114:NleH protein, E coli; D012269:Ribosomal Proteins; C044152:ribosomal protein S3; D012694:Serine; D051550:I-kappa B Kinase