Science · 2006 · 618 citations · 8 references
Life SciencesBiochemistryMolecular BiologyCell SignalingInnate ImmunitySignal TransductionImmune Signaling PathwaysInnate Immune ActivationInnate Immune ModulationInnate Immune ResponseInnate Immune Signaling PathwaysProtein Kinase CascadesActivation Loop RegulationBiological SignalingCovalent Modification Of EnzymesInnate Immunity PathwaysMapk SignalingMitogen-activated Protein Kinase SignalingNuclear Factor Kappa B ActivationNuclear Factor Kappa B Inhibition
Yersinia species use a variety of type III effector proteins to target eukaryotic signaling systems. The effector YopJ inhibits mitogen-activated protein kinase (MAPK) and the nuclear factor kappaB (NFkappaB) signaling pathways used in innate immune response by preventing activation of the family of MAPK kinases (MAPKK). We show that YopJ acted as an acetyltransferase, using acetyl-coenzyme A (CoA) to modify the critical serine and threonine residues in the activation loop of MAPKK6 and thereby blocking phosphorylation. The acetylation on MAPKK6 directly competed with phosphorylation, preventing activation of the modified protein. This covalent modification may be used as a general regulatory mechanism in biological signaling.
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Disruption of Signaling by <i>Yersinia</i> Effector YopJ, a Ubiquitin-Like Protein Protease
Kim Orth, Zhaohui Xu, Mary Beth Mudgett et al. · Science · 2000 · 546 citations