The WW Domain Protein Kibra Acts Upstream of Hippo in Drosophila
The WW Domain Protein Kibra Acts Upstream of Hippo in Drosophila
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DOI：
10.1016/j.devcel.2009.12.013
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发表时间：
2010-02-16
影响因子：
11.8
通讯作者：
Stocker, Hugo
中科院分区：
文献类型：
--
作者：
Baumgartner, Roland;Poernbacher, Ingrid;Stocker, Hugo
保守的河马蛋白激酶途径通过抑制增殖和促进细胞凋亡，在控制器官大小和抑制肿瘤方面发挥着关键作用。然而，由丝氨酸/苏氨酸激酶河马和疣组成的核心激酶级联在磷酸化从而使转录辅助激活因子York kie失活的功能已经得到了很好的证实，但对调节河马信号活性的上游事件却知之甚少。FERM结构域蛋白Expanded和Merlin似乎代表了两个不同的信号分支，它们馈送到河马途径。非典型钙粘蛋白脂肪的信号可能通过扩展发挥作用，但Merlin是如何被调控的仍然难以捉摸。在这里，我们证明了WW结构域蛋白Kibra是河马和Merlin上游的河马信号成分。Kibra与Expanded协同作用，并与Merlin进行物理交互。因此，Kibra主要作用于核心激酶级联上游的Merlin分支，以调节河马信号。
The conserved Hippo kinase pathway plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. Whereas the function of the core kinase cascade, consisting of the serine/threonine kinases Hippo and Warts, in phosphorylating and thereby inactivating the transcriptional coactivator Yorkie is well established, much less is known about the upstream events that regulate Hippo signaling activity. The FERM domain proteins Expanded and Merlin appear to represent two different signaling branches that feed into the Hippo pathway. Signaling by the atypical cadherin Fat may act via Expanded, but how Merlin is regulated has remained elusive. Here, we show that the WW domain protein Kibra is a Hippo signaling component upstream of Hippo and Merlin. Kibra acts synergistically with Expanded, and it physically interacts with Merlin. Thus, Kibra predominantly acts in the Merlin branch upstream of the core kinase cascade to regulate Hippo signaling.