Acetylation of MEK2 and IκB kinase (IKK) activation loop residues by YopJ inhibits signaling

被引:229
作者
Mittal, Rohit
Peak-Chew, Sew-Yeu
McMahon, Harvey T.
机构
[1] MRC, Mol Biol Lab, Cambridge CB2 2QH, England
[2] Tata Inst Fundamental Res, Dept Biol Sci, Bombay 400005, Maharashtra, India
基金
英国医学研究理事会;
关键词
inflammation; MEK;
D O I
10.1073/pnas.0608995103
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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-kappa B 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-kappa B 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.
引用
收藏
页码:18574 / 18579
页数:6
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