GEF-H1 mediated control of NOD1 dependent NF-kappaB activation by Shigella effectors.
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 nucle...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2008-11-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC2583055?pdf=render |
| _version_ | 1819009960221081600 |
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| author | Atsuko Fukazawa Carmen Alonso Kiyotaka Kurachi Sonal Gupta Cammie F Lesser Beth Ann McCormick Hans-Christian Reinecker |
| author_facet | Atsuko Fukazawa Carmen Alonso Kiyotaka Kurachi Sonal Gupta Cammie F Lesser Beth Ann McCormick Hans-Christian Reinecker |
| author_sort | Atsuko Fukazawa |
| collection | DOAJ |
| description | 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-kappaB activation in response to Shigella infection. GEF-H1 interacts with NOD1 and is required for RIP2 dependent NF-kappaB activation by H-Ala-D-gammaGlu-DAP (gammaTriDAP). GEF-H1 is essential for NF-kappaB 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. |
| first_indexed | 2024-12-21T01:04:40Z |
| format | Article |
| id | doaj.art-85eb69c61b9f4a8794b066bd63425aba |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-21T01:04:40Z |
| publishDate | 2008-11-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-85eb69c61b9f4a8794b066bd63425aba2022-12-21T19:21:04ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742008-11-01411e100022810.1371/journal.ppat.1000228GEF-H1 mediated control of NOD1 dependent NF-kappaB activation by Shigella effectors.Atsuko FukazawaCarmen AlonsoKiyotaka KurachiSonal GuptaCammie F LesserBeth Ann McCormickHans-Christian ReineckerShigella 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-kappaB activation in response to Shigella infection. GEF-H1 interacts with NOD1 and is required for RIP2 dependent NF-kappaB activation by H-Ala-D-gammaGlu-DAP (gammaTriDAP). GEF-H1 is essential for NF-kappaB 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.http://europepmc.org/articles/PMC2583055?pdf=render |
| spellingShingle | Atsuko Fukazawa Carmen Alonso Kiyotaka Kurachi Sonal Gupta Cammie F Lesser Beth Ann McCormick Hans-Christian Reinecker GEF-H1 mediated control of NOD1 dependent NF-kappaB activation by Shigella effectors. PLoS Pathogens |
| title | GEF-H1 mediated control of NOD1 dependent NF-kappaB activation by Shigella effectors. |
| title_full | GEF-H1 mediated control of NOD1 dependent NF-kappaB activation by Shigella effectors. |
| title_fullStr | GEF-H1 mediated control of NOD1 dependent NF-kappaB activation by Shigella effectors. |
| title_full_unstemmed | GEF-H1 mediated control of NOD1 dependent NF-kappaB activation by Shigella effectors. |
| title_short | GEF-H1 mediated control of NOD1 dependent NF-kappaB activation by Shigella effectors. |
| title_sort | gef h1 mediated control of nod1 dependent nf kappab activation by shigella effectors |
| url | http://europepmc.org/articles/PMC2583055?pdf=render |
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