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The bacterial protein YopJ abrogates multiple signal transduction pathways that converge on the transcription factor
L K Meijer1, K Schesser, H Wolf-Watz
1Center for Genomics Research, Karolinska Institutet, Stockholm, Sweden.
Abstract:
Bacterially encoded proteins are known to affect eukaryotic signalling pathways and thus cell growth and differentiation. The enteric pathogen Yersinia pseudotuberculosis (YP) can translocate Yersinia outer proteins (Yops) into eukaryotic cells. Recently, MKK proteins have been identified as tentative targets of YopJ-mediated inhibition of ligand receptor-dependent signal transduction in mammalian cells. These results prompted us to assess whether multiple signal transduction pathways and their downstream target genes would also be subject to regulation by YopJ. Here, we show that YopJ effectively blocks the lipopolysaccharide (LPS) receptor, the interleukin (IL)-1beta receptor and the UVC-induced activation of the transcription receptor cAMP response element-binding protein (CREB). In addition, by abrogating the phosphorylation of CREB and thus activating protein (AP)-1-dependent transcription, YopJ can block LPS-induced clonal expansion that is associated with an adaptive immune response. Thus, YopJ interferes with multiple pathways converging on the transcription factor CREB. Our data are discussed in the context of YopJ acting as an antagonist to circumvent innate and adaptive immune responses at multiple levels.
Insights
Yersinia outer protein J (YopJ) inhibits multiple eukaryotic signaling pathways, including those involving lipopolysaccharide and interleukin-1beta receptors. This bacterial protein targets the transcription factor CREB, potentially blocking immune responses.
Area of Science:
- Microbiology
- Immunology
- Cell Biology
Background:
- Bacterial proteins can modulate eukaryotic cell signaling, growth, and differentiation.
- Yersinia pseudotuberculosis (YP) translocates Yersinia outer proteins (Yops) into host cells.
- MKK proteins are potential targets of YopJ in inhibiting ligand receptor-dependent signal transduction.
Purpose of the Study:
- To investigate if YopJ regulates multiple signal transduction pathways and their target genes.
- To understand the broader impact of YopJ on host cell signaling beyond MKK proteins.
Main Methods:
- Assessing the effect of YopJ on lipopolysaccharide (LPS) receptor signaling.
- Evaluating YopJ's impact on interleukin-1beta (IL-1beta) receptor activation.
- Analyzing YopJ's influence on UVC-induced activation of cAMP response element-binding protein (CREB).
Main Results:
- YopJ blocks LPS receptor and IL-1beta receptor signaling.
- YopJ inhibits UVC-induced activation of CREB.
- YopJ abrogates CREB phosphorylation, blocking activating protein-1 (AP-1)-dependent transcription and LPS-induced clonal expansion.
Conclusions:
- YopJ interferes with multiple signaling pathways converging on the transcription factor CREB.
- YopJ acts as an antagonist to circumvent innate and adaptive immune responses.
- Understanding YopJ's mechanism provides insights into bacterial immune evasion strategies.