| Literature DB >> 25731159 |
Koji Taniguchi1, Li-Wha Wu2, Sergei I Grivennikov3, Petrus R de Jong4, Ian Lian5, Fa-Xing Yu6, Kepeng Wang7, Samuel B Ho8, Brigid S Boland9, John T Chang9, William J Sandborn9, Gary Hardiman10, Eyal Raz4, Yoshihiko Maehara11, Akihiko Yoshimura12, Jessica Zucman-Rossi13, Kun-Liang Guan14, Michael Karin15.
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.Entities:
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Year: 2015 PMID： 25731159 PMCID： PMC4447318 DOI： 10.1038/nature14228
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 49.962