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 language | English |
|---|---|
| Pages (from-to) | 1067-1079 |
| Number of pages | 13 |
| Journal | Molecular Microbiology |
| Volume | 28 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jul 8 1998 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Molecular Biology
- Microbiology
Cite this
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. / Schesser, Kurt; Spiik, Ann Kristin; Dukuzumuremyi, Jean Marie; Neurath, Markus F.; Pettersson, Sven; Wolf-Watz, Hans.
In: Molecular Microbiology, Vol. 28, No. 6, 08.07.1998, p. 1067-1079.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The yopJ locus is required for Yersinia-mediated inhibition of NF-κB activation and cytokine expression
T2 - YopJ contains a eukaryotic SH2-like domain that is essential for its repressive activity
AU - Schesser, Kurt
AU - Spiik, Ann Kristin
AU - Dukuzumuremyi, Jean Marie
AU - Neurath, Markus F.
AU - Pettersson, Sven
AU - Wolf-Watz, Hans
PY - 1998/7/8
Y1 - 1998/7/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0031775572&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031775572&partnerID=8YFLogxK
U2 - 10.1046/j.1365-2958.1998.00851.x
DO - 10.1046/j.1365-2958.1998.00851.x
M3 - Article
C2 - 9680199
AN - SCOPUS:0031775572
VL - 28
SP - 1067
EP - 1079
JO - Molecular Microbiology
JF - Molecular Microbiology
SN - 0950-382X
IS - 6
ER -