title: Acetylation of MEK2 and I kappa B kinase (IKK) activation loop residues by YopJ inhibits signaling.
abstract: To overcome host defenses, bacterial pathogens of the genus Yersinia inject specific effector proteins into colonized mammalian cells. One such virulence factor, YopJ, inhibits the host inflammatory response and induces apoptosis of immune cells by blocking multiple signaling pathways, including the MAPK and NF-kappaB pathways. In this study, we show that YopJ exerts its deleterious effects by catalyzing the acetylation of two serine residues in the activation loop of the MAP kinase kinase, MEK2. This covalent modification prevents the phosphorylation of these serine residues that is required for activation of MEK2 and downstream signal propagation. We also show that YopJ causes acetylation of a threonine residue in the activation loop of both the alpha and beta subunits of the NF-kappaB pathway kinase, IKK. These results establish a hitherto uncharacterized mode of action for bacterial toxins and suggest the possibility that serine/threonine acetylation may occur even under nonpathogenic conditions and may be a widespread protein modification regulating protein function in eukaryotic cells.
authors.affiliation: Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom. rohit@mrc-lmb.cam.ac.uk
authors.forename: Rohit
authors.initials: R
authors.lastname: Mittal
authors.forename: Sew-Yeu
authors.initials: SY
authors.lastname: Peak-Chew
authors.forename: Harvey T
authors.initials: HT
authors.lastname: McMahon
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000502:physiology*; D004789:Enzyme Activation / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D048370:MAP Kinase Kinase 2 / Q000378:metabolism*; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D015398:Signal Transduction / Q000502:physiology*; D015007:Yersinia / Q000472:pathogenicity*
chemical_list: D001426:Bacterial Proteins; C109227:YopP protein, Yersinia; C482128:MAP2K2 protein, human; D051550:I-kappa B Kinase; D048370:MAP Kinase Kinase 2