A gp130-Src-YAP module links inflammation to epithelial regeneration.
Nature
; 519(7541): 57-62, 2015 Mar 05.
Article
em En
| MEDLINE
| ID: mdl-25731159
ABSTRACT
Inflammation promotes regeneration of injured tissues through poorly understood mechanisms, some of which involve interleukin (IL)-6 family members, the expression of which is elevated in many diseases including inflammatory bowel diseases and colorectal cancer. Here we show in mice and human cells that gp130, a co-receptor for IL-6 cytokines, triggers activation of YAP and Notch, transcriptional regulators that control tissue growth and regeneration, independently of the gp130 effector STAT3. Through YAP and Notch, intestinal gp130 signalling stimulates epithelial cell proliferation, causes aberrant differentiation and confers resistance to mucosal erosion. gp130 associates with the related tyrosine kinases Src and Yes, which are activated on receptor engagement to phosphorylate YAP and induce its stabilization and nuclear translocation. This signalling module is strongly activated upon mucosal injury to promote healing and maintain barrier function.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Fosfoproteínas
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Regeneração
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Proteínas Proto-Oncogênicas pp60(c-src)
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Proteínas Adaptadoras de Transdução de Sinal
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Células Epiteliais
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Receptor gp130 de Citocina
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Inflamação
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Mucosa Intestinal
Limite:
Animals
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Humans
Idioma:
En
Revista:
Nature
Ano de publicação:
2015
Tipo de documento:
Article