title: S. typhimurium encodes an activator of Rho GTPases that induces membrane ruffling and nuclear responses in host cells.
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.
authors.affiliation: Department of Molecular Genetics and Microbiology, School of Medicine, State University of New York at Stony Brook, 11794-5222, USA.
authors.forename: W D
authors.initials: WD
authors.lastname: Hardt
authors.forename: L M
authors.initials: LM
authors.lastname: Chen
authors.forename: K E
authors.initials: KE
authors.lastname: Schuebel
authors.forename: X R
authors.initials: XR
authors.lastname: Bustelo
authors.forename: J E
authors.initials: JE
authors.lastname: Galán
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D019556:COS Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D002462:Cell Membrane; D002467:Cell Nucleus; D003599:Cytoskeleton; D004789:Enzyme Activation; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020690:GTPase-Activating Proteins; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D011506:Proteins / Q000378:metabolism; D012486:Salmonella typhimurium / Q000472:pathogenicity*; D015398:Signal Transduction; D020764:cdc42 GTP-Binding Protein
chemical_list: D001426:Bacterial Proteins; D018797:Cell Cycle Proteins; D020690:GTPase-Activating Proteins; D011506:Proteins; C103987:SopE protein, Salmonella; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020764:cdc42 GTP-Binding Protein