SASH1 is a scaffold molecule in endothelial TLR4 signaling.
J Immunol
; 191(2): 892-901, 2013 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-23776175
ABSTRACT
Recognition of microbial products by TLRs is critical for mediating innate immune responses to invading pathogens. In this study, we identify a novel scaffold protein in TLR4 signaling called SAM and SH3 domain containing protein 1 (SASH1). Sash1 is expressed across all microvascular beds and functions as a scaffold molecule to independently bind TRAF6, TAK1, IκB kinase α, and IκB kinase ß. This interaction fosters ubiquitination of TRAF6 and TAK1 and promotes LPS-induced NF-κB, JNK, and p38 activation, culminating in increased production of proinflammatory cytokines and increased LPS-induced endothelial migration. Our findings suggest that SASH1 acts to assemble a signaling complex downstream of TLR4 to activate early endothelial responses to receptor activation.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Supressoras de Tumor
/
Células Endoteliais
/
Fator 6 Associado a Receptor de TNF
/
Receptor 4 Toll-Like
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Canadá