STRIPAK integrates upstream signals to initiate the Hippo kinase cascade.,Nature Cell Biology

当前位置： X-MOL 学术 › Nat. Cell Biol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

STRIPAK integrates upstream signals to initiate the Hippo kinase cascade.
Nature Cell Biology ( IF 17.3 ) Pub Date : 2019-12-02 , DOI: 10.1038/s41556-019-0426-y
Rui Chen ₁ , Ruiling Xie _{1,

2} , Zhipeng Meng ₁ , Shenghong Ma ₁ , Kun-Liang Guan ₁

Affiliation

The Hippo pathway plays a critical role in development, tissue homeostasis and organ size; its dysregulation contributes to human diseases. Although MST1/2 and the MAP4Ks are well known as the Hippo kinases, a major open question is how these kinases are regulated by upstream signals. Here we report that STRIPAK integrates upstream signals to control the activities of MST1/2 and the MAP4Ks, thus initiating Hippo signalling. STRIPAK also serves as a master regulator for the STE20 family kinases. Following serum or lysophosphatidic acid stimulation, active RhoA binds and dissociates rhophilin and NF2/Kibra from STRIPAK, thereby inducing the association and dephosphorylation of MST1/2 and MAP4Ks by the STRIPAK phosphatase catalytic subunit PP2AC. Rhophilin suppresses cancer cell growth by activating the Hippo pathway. Our study reveals a RhoA-rhophilin-NF2/Kibra-STRIPAK signalling axis in Hippo regulation, thus addressing the key question of how Hippo signalling is initiated and suggesting a broad and active role for STRIPAK in cellular signalling.

中文翻译：

STRIPAK 整合上游信号以启动 Hippo 激酶级联。

Hippo 通路在发育、组织稳态和器官大小中起关键作用；它的失调会导致人类疾病。尽管 MST1/2 和 MAP4K 被称为 Hippo 激酶，但一个主要的悬而未决的问题是这些激酶如何受上游信号的调节。在这里，我们报告 STRIPAK 整合上游信号来控制 MST1/2 和 MAP4Ks 的活动，从而启动 Hippo 信号传导。STRIPAK 还作为 STE20 家族激酶的主要调节剂。在血清或溶血磷脂酸刺激后，活性 RhoA 结合并从 STRIPAK 中解离 rhophilin 和 NF2/Kibra，从而通过 STRIPAK 磷酸酶催化亚基 PP2AC 诱导 MST1/2 和 MAP4K 的缔合和去磷酸化。Rhophilin 通过激活 Hippo 通路来抑制癌细胞的生长。

更新日期：2019-12-02

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11