Publications

• Serine/threonine acetylation of TGFbeta-activated kinase (TAK1) by Yersinia pestis YopJ inhibits innate immune signaling.

  Paquette N., Conlon J., Sweet C., Rus F., Wilson L., Pereira A., Rosadini C.V., Goutagny N., Weber A.N., Lane W.S., Shaffer S.A., Maniatis S., Fitzgerald K.A., Stuart L., Silverman N.

  The Gram-negative bacteria Yersinia pestis, causative agent of plague, is extremely virulent. One mechanism contributing to Y. pestis virulence is the presence of a type-three secretion system, which injects effector proteins, Yops, directly into immune cells of the infected host. One of these Yop ... >> More

  The Gram-negative bacteria Yersinia pestis, causative agent of plague, is extremely virulent. One mechanism contributing to Y. pestis virulence is the presence of a type-three secretion system, which injects effector proteins, Yops, directly into immune cells of the infected host. One of these Yop proteins, YopJ, is proapoptotic and inhibits mammalian NF-κB and MAP-kinase signal transduction pathways. Although the molecular mechanism remained elusive for some time, recent work has shown that YopJ acts as a serine/threonine acetyl-transferase targeting MAP2 kinases. Using Drosophila as a model system, we find that YopJ inhibits one innate immune NF-κB signaling pathway (IMD) but not the other (Toll). In fact, we show YopJ mediated serine/threonine acetylation and inhibition of dTAK1, the critical MAP3 kinase in the IMD pathway. Acetylation of critical serine/threonine residues in the activation loop of Drosophila TAK1 blocks phosphorylation of the protein and subsequent kinase activation. In addition, studies in mammalian cells show similar modification and inhibition of hTAK1. These data present evidence that TAK1 is a target for YopJ-mediated inhibition. << Less

  Proc. Natl. Acad. Sci. U.S.A. 109:12710-12715(2012) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• A newly discovered post-translational modification--the acetylation of serine and threonine residues.

  Mukherjee S., Hao Y.H., Orth K.

  Recent studies on a bacterial virulence factor, YopJ of Yersinia, have led to the realization that the acetylation of serine and threonine residues could be an important form of post-translational modification in eukaryotes. Although the identification of the machinery used for the addition and re ... >> More

  Recent studies on a bacterial virulence factor, YopJ of Yersinia, have led to the realization that the acetylation of serine and threonine residues could be an important form of post-translational modification in eukaryotes. Although the identification of the machinery used for the addition and removal of acetyl groups on serine or threonine residues is in its infancy, the enzymes thus-far studied provide early insight into the mechanism of this newly discovered post-translational modification, and hint at its potential importance. For example, acetylation can compete with phosphorylation targeted to the same residues and could, therefore, alter the course of signaling pathways. What are the implications for signal transduction in eukaryotes and how widespread could acetylation of serine and threonine prove to be? << Less

  Trends Biochem Sci 32:210-216(2007) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.

• Yersinia YopJ acetylates and inhibits kinase activation by blocking phosphorylation.

  Mukherjee S., Keitany G., Li Y., Wang Y., Ball H.L., Goldsmith E.J., Orth K.

  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 ... >> More

  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. << Less

  Science 312:1211-1214(2006) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.