Innate immune and proinflammatory signals activate the Hippo pathway via a Tak1-STRIPAK-Tao axis.
Innate immune and proinflammatory signals activate the Hippo pathway via a Tak1-STRIPAK-Tao axis.
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DOI：
10.1038/s41467-023-44542-y
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发表时间：
2024-01-02
影响因子：
16.6
通讯作者：
Liu, Bo
中科院分区：
文献类型：
--
作者：
Yang, Yinan;Zhou, Huijing;Huang, Xiawei;Wu, Chengfang;Zheng, Kewei;Deng, Jingrong;Zheng, Yonggang;Wang, Jiahui;Chi, Xiaofeng;Ma, Xianjue;Pan, Huimin;Shen, Rui;Pan, Duojia;Liu, Bo
Hippo通路控制发育、稳态和再生组织生长，并且在各种疾病中经常失调。虽然该途径可以被先天免疫/炎症刺激激活，但其潜在机制尚未完全了解。在这里，我们确定了一个保守的信号级联，导致Hippo通路激活先天免疫/炎症信号。我们发现，Tak 1，在先天免疫/炎症信号传导的关键激酶，激活海马通路诱导溶酶体降解的Cka，一个重要的亚基的STRIPAK PP 2A复合物，抑制海马信号。抑制STRIPAK导致通过Tao-Hpo信号传导激活Hippo通路。我们进一步表明，Tak 1介导的Hippo信号参与了从细胞死亡到吞噬作用和先天免疫记忆的过程。因此，我们的研究结果揭示了先天免疫/炎症信号传导与进化保守的Hippo通路之间的分子联系，从而有助于我们对感染性，炎症性和恶性疾病的理解。进化上保守的Hippo途径调节重要的发育、稳态和再生过程，并参与宿主对病原体的防御。在这里，作者表明，在果蝇和哺乳动物细胞中，先天免疫刺激通过Tak 1激酶发出的通路激活Hippo，并通过STRIPAK-Tao-Hpo信号传导级联到Hippo。
The Hippo pathway controls developmental, homeostatic and regenerative tissue growth, and is frequently dysregulated in various diseases. Although this pathway can be activated by innate immune/inflammatory stimuli, the underlying mechanism is not fully understood. Here, we identify a conserved signaling cascade that leads to Hippo pathway activation by innate immune/inflammatory signals. We show that Tak1, a key kinase in innate immune/inflammatory signaling, activates the Hippo pathway by inducing the lysosomal degradation of Cka, an essential subunit of the STRIPAK PP2A complex that suppresses Hippo signaling. Suppression of STRIPAK results in the activation of Hippo pathway through Tao-Hpo signaling. We further show that Tak1-mediated Hippo signaling is involved in processes ranging from cell death to phagocytosis and innate immune memory. Our findings thus reveal a molecular connection between innate immune/inflammatory signaling and the evolutionally conserved Hippo pathway, thus contributing to our understanding of infectious, inflammatory and malignant diseases. The evolutionally conserved Hippo pathway regulates essential developmental, homeostatic and regenerative processes, and is involved in the host defense against pathogens. Here authors show that in Drosophila Melanogaster and mammalian cells, innate immune stimuli activate Hippo via a pathway emanating from the Tak1 kinase and cascading down to Hippo via STRIPAK-Tao-Hpo signaling.
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影响因子：
--
作者：
Christofi T;Apidianakis Y
通讯作者：
Apidianakis Y
影响因子：
7.7
作者：
Petrignani B;Rommelaere S;Hakim-Mishnaevski K;Masson F;Ramond E;Hilu-Dadia R;Poidevin M;Kondo S;Kurant E;Lemaitre B
通讯作者：
Lemaitre B
DOI：
10.1073/pnas.0812022106
发表时间：
2009-06-16
影响因子：
11.1
作者：
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通讯作者：
Silverman, Neal
影响因子：
64.5
作者：
Dong, Jixin;Feldmann, Georg;Pan, Duojia
通讯作者：
Pan, Duojia
影响因子：
21.3
作者：
Gatica D;Lahiri V;Klionsky DJ
通讯作者：
Klionsky DJ