Global Profiling of PknG Interactions Using a Human Proteome Microarray Reveals Novel Connections with CypA.
Proteomics
; 18(23): e1800265, 2018 12.
Article
em En
| MEDLINE
| ID: mdl-30281201
ABSTRACT
Mycobacterium tuberculosis (Mtb) serine/threonine kinase PknG plays an important role in the Mtb-host interaction by facilitating the survival of Mtb in macrophages. However, the human proteins with which the PknG interacts, and the underlying molecular mechanisms are still largely unknown. In this study, a HuProt array is been applied to globally identify the host proteins to which PknG binds. In this way, 125 interactors are discovered, including a cyclophilin protein, CypA. This interaction between PknG and CypA is validated both in vitro and in vivo, and functional studies show that PknG significantly reduces the protein levels of CypA through phosphorylation, which consequently inhibit the inflammatory response through downregulation of NF-κB and ERK1/2 pathways. Phenotypically, overexpression of PknG reduces cytokine levels and promotes the survival of Mycobacterium smegmatis (Msm) in macrophages. Overall, it is expected that the PknG interactors identified in this study will serve as a useful resource for further systematic studies of the roles that PknG plays in the Mtb-host interactions.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
3_ND
Base de dados:
MEDLINE
Assunto principal:
Proteoma
/
Mycobacterium tuberculosis
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Proteomics
Ano de publicação:
2018
Tipo de documento:
Article