TheSalmonellaTyphimurium effector SteC inhibits Cdc42-mediated signaling through binding to the exchange factor Cdc24 inSaccharomyces cerevisiae
| Autor: | María Molina, John Sondek, Pablo Fernandez-Piñar, Ainel Alemán, Henrik G. Dohlman, Humberto Martín |
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| Rok vydání: | 2012 |
| Předmět: |
Salmonella typhimurium
Saccharomyces cerevisiae Proteins MAP Kinase Signaling System animal diseases Saccharomyces cerevisiae Active Transport Cell Nucleus Cell Cycle Proteins GTPase CDC42 Biology Microbiología Models Biological fluids and secretions Schizosaccharomyces Guanine Nucleotide Exchange Factors Humans cdc42 GTP-Binding Protein Protein kinase A Molecular Biology Cellular localization Effector Articles Cell Biology biochemical phenomena metabolism and nutrition bacterial infections and mycoses biology.organism_classification Signaling Protein Structure Tertiary Mating of yeast Biochemistry bacteria Guanine nucleotide exchange factor biological phenomena cell phenomena and immunity Protein Kinases Signal Transduction |
| Zdroj: | E-Prints Complutense: Archivo Institucional de la UCM Universidad Complutense de Madrid Molecular Biology of the Cell E-Prints Complutense. Archivo Institucional de la UCM instname |
| ISSN: | 1939-4586 1059-1524 |
| Popis: | Expression of the Salmonella effector SteC in yeast leads to down-regulation of the mating and HOG pathways by Cdc42 inhibition. This is mediated by the SteC N-terminal domain through binding to the GEF Cdc24. SteC alters Cdc24 localization and also interacts with human GEF Vav1, suggesting that SteC could target Cdc42 function in host cells. Intracellular survival of Salmonella relies on the activity of proteins translocated into the host cell by type III secretion systems (T3SS). The protein kinase activity of the T3SS effector SteC is required for F-actin remodeling in host cells, although no SteC target has been identified so far. Here we show that expression of the N-terminal non-kinase domain of SteC down-regulates the mating and HOG pathways in Saccharomyces cerevisiae. Epistasis analyses using constitutively active components of these pathways indicate that SteC inhibits signaling at the level of the GTPase Cdc42. We demonstrate that SteC interacts through its N-terminal domain with the catalytic domain of Cdc24, the sole S. cerevisiae Cdc42 guanine nucleotide exchange factor (GEF). SteC also binds to the human Cdc24-like GEF protein Vav1. Moreover, expression of human Cdc42 suppresses growth inhibition caused by SteC. Of interest, the N-terminal SteC domain alters Cdc24 cellular localization, preventing its nuclear accumulation. These data reveal a novel functional domain within SteC, raising the possibility that this effector could also target GTPase function in mammalian cells. Our results also highlight the key role of the Cdc42 switch in yeast mating and HOG pathways and provide a new tool to study the functional consequences of Cdc24 localization. |
| Databáze: | OpenAIRE |
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