GEF-H1 Mediated Control of NOD1 Dependent NF-κB Activation by Shigella Effectors
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GEF-H1 Mediated Control of NOD1 Dependent NF-κB Activation by Shigella Effectors
| Title: | GEF-H1 Mediated Control of NOD1 Dependent NF-κB Activation by Shigella Effectors |
| Author: |
Fukazawa, Atsuko; Alonso, Carmen; Kurachi, Kiyotaka; Gupta, Sonal; Philpott, Dana J.; Lesser, Cammie; McCormick, Beth A.; Reinecker, Hans-Christian
Note: Order does not necessarily reflect citation order of authors. |
| Citation: | Fukazawa, Atsuko, Carmen Alonso, Kiyotaka Kurachi, Sonal Gupta, Cammie F. Lesser, Beth Ann McCormick, and Hans-Christian Reinecker. 2008. GEF-H1 Mediated Control of NOD1 Dependent NF-κB Activation by Shigella Effectors. PLoS Pathogens 4(11): e1000228. |
| Full Text & Related Files: |
2583055.pdf (3.090Mb; PDF) 
|
| Abstract: | Shigella flexneri has evolved the ability to modify host cell function with intracellular active effectors to overcome the intestinal barrier. The detection of these microbial effectors and the initiation of innate immune responses are critical for rapid mucosal defense activation. The guanine nucleotide exchange factor H1 (GEF-H1) mediates RhoA activation required for cell invasion by the enteroinvasive pathogen Shigella flexneri. Surprisingly, GEF-H1 is requisite for NF-κB activation in response to Shigella infection. GEF-H1 interacts with NOD1 and is required for RIP2 dependent NF-κB activation by H-Ala-D-γGlu-DAP (γTriDAP). GEF-H1 is essential for NF-κB activation by the Shigella effectors IpgB2 and OspB, which were found to signal in a NOD1 and RhoA Kinase (ROCK) dependent manner. Our results demonstrate that GEF-H1 is a critical component of cellular defenses forming an intracellular sensing system with NOD1 for the detection of microbial effectors during cell invasion by pathogens. |
| Published Version: | doi:10.1371/journal.ppat.1000228 |
| Other Sources: | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2583055/pdf/ |
| Terms of Use: | This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA |
| Citable link to this page: | http://nrs.harvard.edu/urn-3:HUL.InstRepos:4879197 |
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