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PLoS Pathog. 2009 Sep;5(9):e1000595. doi: 10.1371/journal.ppat.1000595. Epub 2009 Sep 25.

Selective inhibition of type III secretion activated signaling by the Salmonella effector AvrA.

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Section of Microbial Pathogenesis, Yale University School of Medicine, New Haven, Connecticut, United States of America.


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.

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