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Bacillus bombysepticus α-Toxin Binding to G Protein-Coupled Receptor Kinase 2 Regulates cAMP/PKA Signaling Pathway to Induce Host Death.
Lin, Ping; Cheng, Tingcai; Ma, Sanyuan; Gao, Junping; Jin, Shengkai; Jiang, Liang; Xia, Qingyou.
Afiliación
  • Lin P; State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, P. R. China.
  • Cheng T; State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, P. R. China.
  • Ma S; State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, P. R. China.
  • Gao J; State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, P. R. China.
  • Jin S; State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, P. R. China.
  • Jiang L; State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, P. R. China.
  • Xia Q; State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, P. R. China.
PLoS Pathog ; 12(3): e1005527, 2016 Mar.
Article en En | MEDLINE | ID: mdl-27022742
Bacterial pathogens and their toxins target host receptors, leading to aberrant behavior or host death by changing signaling events through subversion of host intracellular cAMP level. This is an efficient and widespread mechanism of microbial pathogenesis. Previous studies describe toxins that increase cAMP in host cells, resulting in death through G protein-coupled receptor (GPCR) signaling pathways by influencing adenylyl cyclase or G protein activity. G protein-coupled receptor kinase 2 (GRK2) has a central role in regulation of GPCR desensitization. However, little information is available about the pathogenic mechanisms of toxins associated with GRK2. Here, we reported a new bacterial toxin-Bacillus bombysepticus (Bb) α-toxin that was lethal to host. We showed that Bb α-toxin interacted with BmGRK2. The data demonstrated that Bb α-toxin directly bound to BmGRK2 to promote death by affecting GPCR signaling pathways. This mechanism involved stimulation of Gαs, increase level of cAMP and activation of protein kinase A (PKA). Activated cAMP/PKA signal transduction altered downstream effectors that affected homeostasis and fundamental biological processes, disturbing the structural and functional integrity of cells, resulting in death. Preventing cAMP/PKA signaling transduction by inhibitions (NF449 or H-89) substantially reduced the pathogenicity of Bb α-toxin. The discovery of a toxin-induced host death specifically linked to GRK2 mediated signaling pathway suggested a new model for bacterial toxin action. Characterization of host genes whose expression and function are regulated by Bb α-toxin and GRK2 will offer a deeper understanding of the pathogenesis of infectious diseases caused by pathogens that elevate cAMP.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bacillus / Toxinas Bacterianas / Transducción de Señal / Proteínas Quinasas Dependientes de AMP Cíclico / Quinasas de Receptores Acoplados a Proteína-G Límite: Animals / Humans Idioma: En Revista: PLoS Pathog Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Bacillus / Toxinas Bacterianas / Transducción de Señal / Proteínas Quinasas Dependientes de AMP Cíclico / Quinasas de Receptores Acoplados a Proteína-G Límite: Animals / Humans Idioma: En Revista: PLoS Pathog Año: 2016 Tipo del documento: Article Pais de publicación: Estados Unidos