An Evolutionarily Conserved PLC-PKD-TFEB Pathway for Host Defense.
Cell Rep
; 15(8): 1728-42, 2016 05 24.
Article
em En
| MEDLINE
| ID: mdl-27184844
ABSTRACT
The mechanisms that tightly control the transcription of host defense genes have not been fully elucidated. We previously identified TFEB as a transcription factor important for host defense, but the mechanisms that regulate TFEB during infection remained unknown. Here, we used C. elegans to discover a pathway that activates TFEB during infection. Gene dkf-1, which encodes a homolog of protein kinase D (PKD), was required for TFEB activation in nematodes infected with Staphylococcus aureus. Conversely, pharmacological activation of PKD was sufficient to activate TFEB. Furthermore, phospholipase C (PLC) gene plc-1 was also required for TFEB activation, downstream of Gαq homolog egl-30 and upstream of dkf-1. Using reverse and chemical genetics, we discovered a similar PLC-PKD-TFEB axis in Salmonella-infected mouse macrophages. In addition, PKCα was required in macrophages. These observations reveal a previously unknown host defense signaling pathway, which has been conserved across one billion years of evolution.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fosfolipases Tipo C
/
Proteína Quinase C
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Transdução de Sinais
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Caenorhabditis elegans
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Evolução Molecular
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Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos
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Interações Hospedeiro-Patógeno
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article