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Yersinia effector YopJ inhibits yeast MAPK signaling pathways by an evolutionarily conserved mechanism
Sara Yoon1, Zhengchang Liu, Yvonne Eyobo
1Department of Molecular Biology, University of Texas Southwestern Medical School, Dallas 75390-9148, USA.
Abstract:
Yersinia effector, YopJ, inhibits the innate immune response by blocking MAP kinase and NFkappaB signaling pathways in mammalian cells. Herein, YopJ is shown to disrupt the MAP kinase signaling pathways in Saccharomyces cerevisiae. Expression of YopJ in yeast blocks the ability of yeast to respond to alpha factor by disrupting activation of the pheromone signaling pathway upstream of the activation of the MAPK Fus3p. YopJ also blocks the high osmolarity growth (HOG) MAP kinase pathway in yeast upstream of the activation of the MAPK Hog1p. YopJ is proposed to block the MAP kinase pathways in yeast in a similar manner to the way it blocks mammalian signaling pathways, implicating that a novel, evolutionarily conserved mechanism of regulation is utilized for signal transduction by these pathways.
Insights
The Yersinia effector YopJ disrupts yeast MAP kinase pathways, similar to its action in mammals. This suggests a conserved mechanism regulating cell signaling across species.
Area of Science:
- Microbiology
- Cell Biology
- Molecular Biology
Background:
- Yersinia effector YopJ inhibits mammalian innate immunity by blocking MAP kinase (MAPK) and NF-kappaB signaling.
- Understanding YopJ's mechanism in a simpler model organism can reveal conserved regulatory principles.
Purpose of the Study:
- To investigate the effect of Yersinia effector YopJ on MAP kinase signaling pathways in Saccharomyces cerevisiae (yeast).
- To determine if YopJ's inhibitory function in yeast is conserved compared to its known function in mammalian cells.
Main Methods:
- Yeast strains were engineered to express Yersinia effector YopJ.
- Specific MAP kinase pathways, including the pheromone response pathway and the high osmolarity growth (HOG) pathway, were analyzed.
- The activation of key MAP kinases (Fus3p and Hog1p) was assessed in the presence of YopJ.
Main Results:
- YopJ expression in yeast blocked the pheromone signaling pathway upstream of Fus3p activation in response to alpha factor.
- YopJ also inhibited the HOG pathway upstream of Hog1p activation.
- These findings indicate YopJ disrupts MAP kinase cascades in yeast.
Conclusions:
- Yersinia effector YopJ interferes with yeast MAP kinase pathways, analogous to its effect on mammalian signaling.
- This suggests a conserved, evolutionarily ancient mechanism for regulating signal transduction pathways by YopJ.
- The study implicates a novel regulatory mechanism conserved across kingdoms for signal transduction.