Serine/threonine acetylation of TGFbeta-activated kinase (TAK1) by Yersinia pestis YopJ inhibits innate immune signaling
UMass Chan Affiliations
Proteomics and Mass Spectrometry Facility, Department of Biochemistry and Molecular PharmacologyDepartment of Department of Medicine, Division of Infectious Diseases and Immunology
Document Type
Journal ArticlePublication Date
2012-07-31Keywords
AcetylationAnimals
Bacterial Proteins
Drosophila melanogaster
HEK293 Cells
Humans
*Immunity, Innate
MAP Kinase Kinase Kinases
*MAP Kinase Signaling System
NF-kappa BPlagueSerine O-AcetyltransferaseYersinia pestisImmunology and Infectious Disease
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Show full item recordAbstract
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-kappaB 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-kappaB 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.Source
Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):12710-5. doi: 10.1073/pnas.1008203109. Link to article on publisher's siteDOI
10.1073/pnas.1008203109Permanent Link to this Item
http://hdl.handle.net/20.500.14038/34919PubMed ID
22802624Notes
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1008203109/-/DCSupplemental.Related Resources
Link to Article in PubMedRights
Publisher PDF posted as allowed by the publisher's author rights policy at http://www.pnas.org/site/aboutpnas/authorfaq.xhtml.Scopus Count
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