IKKß regulates essential functions of the vascular endothelium through kinase-dependent and -independent pathways.
Nat Commun
; 2: 318, 2011.
Article
em En
| MEDLINE
| ID: mdl-21587235
ABSTRACT
Vascular endothelium provides a selective barrier between the blood and tissues, participates in wound healing and angiogenesis, and regulates tissue recruitment of inflammatory cells. Nuclear factor (NF)-κB transcription factors are pivotal regulators of survival and inflammation, and have been suggested as potential therapeutic targets in cancer and inflammatory diseases. Here we show that mice lacking IKKß, the primary kinase mediating NF-κB activation, are smaller than littermates and born at less than the expected Mendelian frequency in association with hypotrophic and hypovascular placentae. IKKß-deleted endothelium manifests increased vascular permeability and reduced migration. Surprisingly, we find that these defects result from loss of kinase-independent effects of IKKß on activation of the serine-threonine kinase, Akt. Together, these data demonstrate essential roles for IKKß in regulating endothelial permeability and migration, as well as an unanticipated connection between IKKß and Akt signalling.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Endotélio Vascular
/
Transdução de Sinais
/
Quinase I-kappa B
/
Proteínas Proto-Oncogênicas c-akt
Limite:
Animals
Idioma:
En
Revista:
Nat Commun
Assunto da revista:
BIOLOGIA
/
CIENCIA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos