A gp130-Src-YAP module links inflammation to epithelial regeneration.
A gp130-Src-YAP module links inflammation to epithelial regeneration.
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DOI：
10.1038/nature14228
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发表时间：
2015-03-05
期刊：
影响因子：
64.8
通讯作者：
Karin, Michael
中科院分区：
文献类型：
--
作者：
Taniguchi, Koji;Wu, Li-Wha;Grivennikov, Sergei I.;de Jong, Petrus R.;Lian, Ian;Yu, Fa-Xing;Wang, Kepeng;Ho, Samuel B.;Boland, Brigid S.;Chang, John T.;Sandborn, William J.;Hardiman, Gary;Raz, Eyal;Maehara, Yoshihiko;Yoshimura, Akihiko;Zucman-Rossi, Jessica;Guan, Kun-Liang;Karin, Michael
炎症通过知之甚少的机制促进损伤组织的再生，其中一些机制涉及白细胞介素（IL）-6家族成员，其表达在许多疾病中升高，包括炎症性肠病（IBD）和结直肠癌（CRC）。我们发现，gp 130，IL-6细胞因子的共受体，触发激活雅普和Notch，转录调节控制组织生长和再生，独立于经典的gp 130效应STAT 3。通过雅普和Notch，肠道gp 130信号刺激上皮细胞增殖，导致异常分化并赋予对粘膜糜烂的抵抗力。gp 130与相关的酪氨酸激酶Src和Yes结合，Src和Yes在受体结合时被激活以磷酸化雅普并诱导其稳定化和核转位。该信号传导模块在粘膜损伤时被强烈激活以促进愈合并维持屏障功能。
Inflammation promotes regeneration of injured tissues through poorly understood mechanisms, some of which involve interleukin (IL)-6 family members whose expression is elevated in many diseases, including inflammatory bowel diseases (IBD) and colorectal cancer (CRC). We show 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 classic gp130 effector STAT3. Through YAP and Notch, intestinal gp130 signaling 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 upon receptor engagement to phosphorylate YAP and induce its stabilization and nuclear translocation. This signaling module is strongly activated upon mucosal injury to promote healing and maintain barrier function.
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影响因子：
3.7
作者：
Gordon M;El-Kalla M;Zhao Y;Fiteih Y;Law J;Volodko N;Anwar-Mohamed A;El-Kadi AO;Liu L;Odenbach J;Thiesen A;Onyskiw C;Ghazaleh HA;Park J;Lee SB;Yu VC;Fernandez-Patron C;Alexander RT;Wine E;Baksh S
通讯作者：
Baksh S
DOI：
10.1038/nrd4161
发表时间：
2014-01
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.5
作者：
Azzolin, Luca;Panciera, Tito;Piccolo, Stefano
通讯作者：
Piccolo, Stefano
影响因子：
4.8
作者：
Madison, BB;Dunbar, L;Gumucio, DL
通讯作者：
Gumucio, DL
影响因子：
6.5
作者：
Hu, Hsiao-Tang;Huang, Yi-Hsien;Wu, Li-Wha
通讯作者：
Wu, Li-Wha