The yopJ locus is required for Yersinia-mediated inhibition of NF-κB activation and cytokine expression: YopJ contains a eukaryotic SH2-like domain that is essential for its repressive activity

Kurt Schesser, Ann Kristin Spiik, Jean Marie Dukuzumuremyi, Markus F. Neurath, Sven Pettersson, Hans Wolf-Watz

Research output: Contribution to journalArticle

215 Scopus citations

Abstract

Upon exposure to bacteria, eukaryotic cells activate signalling pathways that result in the increased expression of several defence-related genes. Here, we report that the yopJ locus of the enteropathogen Yersinia pseudotuberculosis encodes a protein that inhibits the activation of NF-κB transcription factors by a mechanism(s), which prevents the phosphorylation and subsequent degradation of the inhibitor protein IκB. Consequently, eukaryotic cells infected with YopJ-expressing Yersinia become impaired in NF-κBdependent cytokine expression. In addition, the blockage of inducible cytokine production coincides with yopJ-dependent induction of apoptosis. Interestingly, the YopJ protein contains a region that resembles a src homology domain 2 (SH2), and we show that a wild-type version of this motif is required for YopJ activity in suppressing cytokine expression and inducing apoptosis. As SH2 domains are found in several eukaryotic signalling proteins, we propose that YopJ, which we show is delivered into the cytoplasm of infected cells, interacts directly with signalling proteins involved in inductive cytokine expression. The repressive activity of YopJ on the expression of inflammatory mediators may account for the lack of an inflammatory host response observed in experimental yersiniosis. YopJ-like activity may also be a common feature of commensal bacteria that, like Yersinia, do not provoke a host inflammatory response.

Original languageEnglish (US)
Pages (from-to)1067-1079
Number of pages13
JournalMolecular Microbiology
Volume28
Issue number6
DOIs
StatePublished - Jul 8 1998
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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