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CrkII/Abl phosphorylation cascade is critical for NLRC4 inflammasome activity and is blocked by Pseudomonas aeruginosa ExoT
Type 3 Secretion System (T3SS) is a highly conserved virulence structure that plays an essential role in the pathogenesis of many Gram-negative pathogenic bacteria, including Pseudomonas aeruginosa. Exotoxin T (ExoT) is the only T3SS effector protein that is expressed in all T3SS-expressing P. aerug...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8917168/ https://www.ncbi.nlm.nih.gov/pubmed/35277504 http://dx.doi.org/10.1038/s41467-022-28967-5 |
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author | Mohamed, Mohamed F. Gupta, Kajal Goldufsky, Josef W. Roy, Ruchi Callaghan, Lauren T. Wetzel, Dawn M. Kuzel, Timothy M. Reiser, Jochen Shafikhani, Sasha H. |
author_facet | Mohamed, Mohamed F. Gupta, Kajal Goldufsky, Josef W. Roy, Ruchi Callaghan, Lauren T. Wetzel, Dawn M. Kuzel, Timothy M. Reiser, Jochen Shafikhani, Sasha H. |
author_sort | Mohamed, Mohamed F. |
collection | PubMed |
description | Type 3 Secretion System (T3SS) is a highly conserved virulence structure that plays an essential role in the pathogenesis of many Gram-negative pathogenic bacteria, including Pseudomonas aeruginosa. Exotoxin T (ExoT) is the only T3SS effector protein that is expressed in all T3SS-expressing P. aeruginosa strains. Here we show that T3SS recognition leads to a rapid phosphorylation cascade involving Abl / PKCδ / NLRC4, which results in NLRC4 inflammasome activation, culminating in inflammatory responses that limit P. aeruginosa infection in wounds. We further show that ExoT functions as the main anti-inflammatory agent for P. aeruginosa in that it blocks the phosphorylation cascade through Abl / PKCδ / NLRC4 by targeting CrkII, which we further demonstrate to be important for Abl transactivation and NLRC4 inflammasome activation in response to T3SS and P. aeruginosa infection. |
format | Online Article Text |
id | pubmed-8917168 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-89171682022-04-01 CrkII/Abl phosphorylation cascade is critical for NLRC4 inflammasome activity and is blocked by Pseudomonas aeruginosa ExoT Mohamed, Mohamed F. Gupta, Kajal Goldufsky, Josef W. Roy, Ruchi Callaghan, Lauren T. Wetzel, Dawn M. Kuzel, Timothy M. Reiser, Jochen Shafikhani, Sasha H. Nat Commun Article Type 3 Secretion System (T3SS) is a highly conserved virulence structure that plays an essential role in the pathogenesis of many Gram-negative pathogenic bacteria, including Pseudomonas aeruginosa. Exotoxin T (ExoT) is the only T3SS effector protein that is expressed in all T3SS-expressing P. aeruginosa strains. Here we show that T3SS recognition leads to a rapid phosphorylation cascade involving Abl / PKCδ / NLRC4, which results in NLRC4 inflammasome activation, culminating in inflammatory responses that limit P. aeruginosa infection in wounds. We further show that ExoT functions as the main anti-inflammatory agent for P. aeruginosa in that it blocks the phosphorylation cascade through Abl / PKCδ / NLRC4 by targeting CrkII, which we further demonstrate to be important for Abl transactivation and NLRC4 inflammasome activation in response to T3SS and P. aeruginosa infection. Nature Publishing Group UK 2022-03-11 /pmc/articles/PMC8917168/ /pubmed/35277504 http://dx.doi.org/10.1038/s41467-022-28967-5 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Mohamed, Mohamed F. Gupta, Kajal Goldufsky, Josef W. Roy, Ruchi Callaghan, Lauren T. Wetzel, Dawn M. Kuzel, Timothy M. Reiser, Jochen Shafikhani, Sasha H. CrkII/Abl phosphorylation cascade is critical for NLRC4 inflammasome activity and is blocked by Pseudomonas aeruginosa ExoT |
title | CrkII/Abl phosphorylation cascade is critical for NLRC4 inflammasome activity and is blocked by Pseudomonas aeruginosa ExoT |
title_full | CrkII/Abl phosphorylation cascade is critical for NLRC4 inflammasome activity and is blocked by Pseudomonas aeruginosa ExoT |
title_fullStr | CrkII/Abl phosphorylation cascade is critical for NLRC4 inflammasome activity and is blocked by Pseudomonas aeruginosa ExoT |
title_full_unstemmed | CrkII/Abl phosphorylation cascade is critical for NLRC4 inflammasome activity and is blocked by Pseudomonas aeruginosa ExoT |
title_short | CrkII/Abl phosphorylation cascade is critical for NLRC4 inflammasome activity and is blocked by Pseudomonas aeruginosa ExoT |
title_sort | crkii/abl phosphorylation cascade is critical for nlrc4 inflammasome activity and is blocked by pseudomonas aeruginosa exot |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8917168/ https://www.ncbi.nlm.nih.gov/pubmed/35277504 http://dx.doi.org/10.1038/s41467-022-28967-5 |
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