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, 93 (5), 815-26

S. Typhimurium Encodes an Activator of Rho GTPases That Induces Membrane Ruffling and Nuclear Responses in Host Cells

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S. Typhimurium Encodes an Activator of Rho GTPases That Induces Membrane Ruffling and Nuclear Responses in Host Cells

W D Hardt et al. Cell.

Abstract

S. typhimurium stimulates signaling pathways leading to membrane ruffling, actin cytoskeleton rearrangements, and nuclear responses. The stimulation requires a protein secretion system (type III) that translocates bacterial proteins into the host cell. We show that SopE, a substrate of this secretion system, stimulates cytoskeletal reorganization and JNK activation in a CDC42- and Rac-1-dependent manner. A lambda gt11 cDNA library screen for proteins that interact with SopE identified Rac-1 and CDC42. Furthermore, purified SopE was shown to stimulate GDP/GTP nucleotide exchange in several Rho GTPases in vitro, including Rac-1 and CDC42. These findings establish a paradigm for microbial stimulation of cellular responses in which the pathogen induces signaling events by directly engaging the signaling machinery within the host cell.

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