ß-arrestin 2 regulates Toll-like receptor 4-mediated apoptotic signalling through glycogen synthase kinase-3ß.
Immunology
; 130(4): 556-63, 2010 Aug.
Article
em En
| MEDLINE
| ID: mdl-20497256
ABSTRACT
Toll-like receptor 4 (TLR4), a key member of the TLR family, has been well characterized by its function in the induction of inflammatory products of innate immunity. However, the involvement of TLR4 in a variety of apoptotic events by an unknown mechanism has been the focus of great interest. Our investigation found that TLR4 promoted apoptotic signalling by affecting the glycogen synthase kinase-3beta (GSK-3beta) pathway in a serum-deprivation-induced apoptotic paradigm. Serum deprivation induces GSK-3beta activation in a pathway that leads to subsequent cell apoptosis. Intriguingly, this apoptotic cascade is amplified in presence of TLR4 but greatly attenuated by beta-arrestin 2, another critical molecule implicated in TLR4-mediated immune responses. Our data suggest that the association of beta-arrestin 2 with GSK-3beta contributes to the stabilization of phospho-GSK-3beta, an inactive form of GSK-3beta. It becomes a critical determinant for the attenuation of TLR4-initiated apoptosis by beta-arrestin 2. Taken together, we demonstrate that the TLR4 possesses the capability of accelerating GSK-3beta activation thereby deteriorating serum-deprivation-induced apoptosis; beta-arrestin 2 represents an inhibitory effect on the TLR4-mediated apoptotic cascade, through controlling the homeostasis of activation and inactivation of GSK-3beta.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Apoptose
/
Arrestinas
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Quinase 3 da Glicogênio Sintase
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Receptor 4 Toll-Like
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Immunology
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
China