ArticleThe Journal of biological chemistry2009
The activities of the Yersinia protein kinase A (YpkA) and outer protein J (YopJ) virulence factors converge on an eIF2alpha kinase.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- Bacterial effector kinases and strategies to identify their target host substrates.Frontiers in microbiology · 2023Review
- Vaccination against Bacterial Infections: Challenges, Progress, and New Approaches with a Focus on Intracellular Bacteria.Vaccines · 2022Review
- Heightened Virulence ofInfection and immunity · 2021Article
- Article
- Hiding in Plain Sight: Formation and Function of Stress Granules During Microbial Infection of Mammalian Cells.Frontiers in molecular biosciences · 2021Review
- Redundant and Cooperative Roles for Yersinia pestis Yop Effectors in the Inhibition of Human Neutrophil Exocytic Responses Revealed by Gain-of-Function Approach.Infection and immunity · 2020Article
- Chromosomally-EncodedFrontiers in cellular and infection microbiology · 2019Article
- The eIF2α Kinase Heme-Regulated Inhibitor Protects the Host from Infection by Regulating Intracellular Pathogen Trafficking.Infection and immunity · 2018Article
- Comparative and network-based proteomic analysis of low dose ethanol- and lipopolysaccharide-induced macrophages.PloS one · 2018Article
- Analysis of differentially expressed proteins in Yersinia enterocolitica-infected HeLa cells.Biochimica et biophysica acta · 2016Article
- Structural insight into effector proteins of Gram-negative bacterial pathogens that modulate the phosphoproteome of their host.Protein science : a publication of the Protein Society · 2015Review
- The Yersinia pestis type III secretion system: expression, assembly and role in the evasion of host defenses.Immunologic research · 2013Review
- The host-encoded Heme Regulated Inhibitor (HRI) facilitates virulence-associated activities of bacterial pathogens.PloS one · 2013Article
- Eukaryotic initiation factor 2 (eIF2) signaling regulates proinflammatory cytokine expression and bacterial invasion.The Journal of biological chemistry · 2012Article
- Staphylococcal PknB as the first prokaryotic representative of the proline-directed kinases.PloS one · 2010Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The Yersinia protein kinase A (YpkA) and outer protein J (YopJ) are co-expressed from a single transcript and are injected directly into eukaryotic cells by the plague bacterium Yersinia pestis. When overexpressed in vertebrate or yeast cells, YpkA disrupts the actin-based cytoskeletal system by an unknown mechanism, whereas YopJ obstructs inductive chemokine expression by inhibiting MAPK and NF-kappaB signaling. Previously, we showed that the fission yeast Schizosaccharomyces pombe was sensitive to the kinase activity of YpkA. Here, we screened yeast for cellular processes important for YpkA activity and found that the eIF2alpha kinases mollify the toxicity imparted by the kinase activity of YpkA. Specifically, strains lacking the eIF2alpha kinase Hri2 were particularly sensitive to YpkA. Unexpectedly, the activity of YopJ, which conferred a phenotype consistent with its inhibitory effect on MAPK signaling, was also found to be dependent on Hri2. When expressed in S. pombe, YopJ sensitized cells to osmotic and oxidative stresses through a Hri2-dependent mechanism. However, when co-expressed with YpkA, YopJ protected cells from YpkA-mediated toxicity, and this protection was entirely dependent on Hri2. In contrast, YopJ did not confer protection against the toxic effects of the Yersinia virulence factor YopE. These findings are the first to functionally link YpkA and YopJ and suggest that eIF2alpha kinases, which are critically important in antiviral defenses and protection against environmental stresses, also play a role in bacterial virulence.
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