Notch signaling suppresses p38 MAPK activity via induction of MKP-1 in myogenesis
Notch signaling suppresses p38 MAPK activity via induction of MKP-1 in myogenesis
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DOI：
10.1074/jbc.m607630200
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发表时间：
2007-02-02
影响因子：
4.8
通讯作者：
Nishida, Eisuke
中科院分区：
文献类型：
--
作者：
Kondoh, Kunio;Sunadome, Kazunori;Nishida, Eisuke
细胞内信号通路之间的交叉对话对于调节细胞命运决定和细胞对细胞外信号的反应非常重要。Notch信号通路和MAPK信号通路在许多生物学过程中都发挥着重要作用，其中Notch信号通路与ERK信号通路相互作用。然而，它与其他MAPK通路的相互作用是未知的。在这里，我们表明，在C2 C12细胞中的Notch信号激活抑制p38 MAPK的活性，抑制肌生成。我们的研究结果表明，Notch特异性地诱导MKP-1的表达，MKP-1是双特异性MAPK磷酸酶的成员，其直接使p38失活以负调节C2 C12肌生成。Notch诱导的MKP-1的表达依赖于RBP-J。此外，通过短干扰RNA抑制MKP-1的表达抑制了p38失活，并部分挽救了肌生成的负调控。这些结果揭示了Notch途径和p38 MAPK途径之间的新的串扰，其由MKP-1的Notch诱导介导。
Cross-talks among intracellular signaling pathways are important for the regulation of cell fate decisions and cellular responses to extracellular signals. Both the Notch pathway and the MAPK pathways play important roles in many biological processes, and the Notch pathway has been shown to interact with the ERK-type MAPK pathway. However, its interaction with the other MAPK pathways is unknown. Here we show that Notch signaling activation in C2C12 cells suppresses the activity of p38 MAPK to inhibit myogenesis. Our results show that Notch specifically induces expression of MKP-1, a member of the dual-specificity MAPK phosphatase, which directly inactivates p38 to negatively regulate C2C12 myogenesis. The Notch-induced expression of MKP-1 is shown to depend on RBP-J. Moreover, inhibition of MKP-1 expression by short interfering RNA suppresses p38 inactivation and partially rescues the negative regulation of myogenesis. These results reveal a novel cross-talk between the Notch pathway and the p38 MAPK pathway that is mediated by Notch induction of MKP-1.