Abstract
Salmonella enterica utilizes a type III secretion system (TTSS) encoded in its pathogenicity island 1 to mediate its initial interactions with intestinal epithelial cells, which are characterized by the stimulation of actin cytoskeleton reorganization and a profound reprogramming of gene expression. These responses result from the stimulation of Rho-family GTPases and downstream signaling pathways by specific effector proteins delivered by this TTSS. We show here that AvrA, an effector protein of this TTSS, specifically inhibits the Salmonella-induced activation of the JNK pathway through its interaction with MKK7, although it does not interfere with the bacterial infection-induced NF-kappaB activation. We also show that AvrA is phosphorylated at evolutionary conserved residues by a TTSS-effector-activated ERK pathway. This interplay between effector proteins delivered by the same TTSS highlights the remarkable complexity of these systems.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Bacterial Proteins / genetics
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Bacterial Proteins / metabolism
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Bacterial Proteins / physiology*
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Cell Line
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Humans
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JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
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JNK Mitogen-Activated Protein Kinases / metabolism
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MAP Kinase Kinase 7 / metabolism
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Mutation
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NF-kappa B / metabolism
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Phosphorylation
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism
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Salmonella Infections / metabolism
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Salmonella Infections / microbiology*
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Salmonella typhimurium / genetics
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Salmonella typhimurium / metabolism
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Salmonella typhimurium / pathogenicity
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Salmonella typhimurium / physiology*
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Secretory Pathway
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Signal Transduction
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Two-Hybrid System Techniques
Substances
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AvrA protein, Salmonella enterica
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Bacterial Proteins
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NF-kappa B
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Spi1 protein, Salmonella
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Extracellular Signal-Regulated MAP Kinases
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JNK Mitogen-Activated Protein Kinases
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MAP Kinase Kinase 7
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MAP2K7 protein, human