S. typhimurium encodes an activator of Rho GTPases that induces membrane ruffling and nuclear responses in host cells.
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.
Hardt
W D
WD
Department of Molecular Genetics and Microbiology, School of Medicine, State University of New York at Stony Brook, 11794-5222, USA.
Chen
L M
LM
Schuebel
K E
KE
Bustelo
X R
XR
Galán
J E
JE
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
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