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PMID:9630225
| Citation |
Hardt, WD, Chen, LM, Schuebel, KE, Bustelo, XR and Galán, JE (1998) S. typhimurium encodes an activator of Rho GTPases that induces membrane ruffling and nuclear responses in host cells. Cell 93:815-26 |
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| 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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| Keywords |
Animals; Bacterial Proteins/metabolism; COS Cells; Calcium-Calmodulin-Dependent Protein Kinases/metabolism; Cell Cycle Proteins/metabolism; Cell Membrane; Cell Nucleus; Cytoskeleton; Enzyme Activation; GTP Phosphohydrolases/metabolism; GTP-Binding Proteins/metabolism; GTPase-Activating Proteins; Guanosine Diphosphate/metabolism; Guanosine Triphosphate/metabolism; HeLa Cells; Humans; JNK Mitogen-Activated Protein Kinases; Mitogen-Activated Protein Kinases; Proteins/metabolism; Salmonella typhimurium/pathogenicity; Signal Transduction; cdc42 GTP-Binding Protein |
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Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0007256: activation of JNKK activity |
ECO:0000314: |
P |
Figure 2. SopE Induces JNK Activation. A vector containing JNK and a vector containing SopE were inserted into COS-1 cells and activities were measured in an immunocomplex kinase assay. The increased activity of JNK in the presence of SopE was seen using immunoblot analyses. |
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