Kibra is a regulator of the Salvador/Warts/Hippo signaling network.
Kibra is a regulator of the Salvador/Warts/Hippo signaling network.
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DOI：
10.1016/j.devcel.2009.12.011
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发表时间：
2010-02-16
影响因子：
11.8
通讯作者：
Tapon N
中科院分区：
文献类型：
--
作者：
Genevet A;Wehr MC;Brain R;Thompson BJ;Tapon N
萨尔瓦多(SAV)/疣(WTS)/河马(HPO)(SWH)网络通过抑制细胞增殖和促进细胞凋亡来控制组织生长。该途径的核心是MST和LATS家族的激酶级联反应，最终使YAP/York kie(Yki)转录共激活因子磷酸化并失活。FERM结构域蛋白Merlin(Mer)和Expanded(Ex)代表一种上游调控方式，控制途径活性。在这里，我们将Kibra确定为SWH网络的成员。Kibra与Mer和Ex共同定位和关联，也促进Mer/Ex协会。此外，Kibra/Mer关联在人类细胞中是保守的。最后，Kibra与WTS的复合体和Kibra在组织培养细胞中的缺失诱导了yki磷酸化的显著降低，而不影响yki/WTS的相互作用。我们认为Kibra是促进SWH途径活性的顶端支架的一部分。►萨尔瓦多/河马/疣网络限制组织大小►我们确定支架蛋白Kibra是SWH上游调节因子►Kibra通过与多个途径成员络合促进SWH活性
The Salvador (Sav)/Warts (Wts)/Hippo (Hpo) (SWH) network controls tissue growth by inhibiting cell proliferation and promoting apoptosis. The core of the pathway consists of a MST and LATS family kinase cascade that ultimately phosphorylates and inactivates the YAP/Yorkie (Yki) transcription coactivator. The FERM domain proteins Merlin (Mer) and Expanded (Ex) represent one mode of upstream regulation controlling pathway activity. Here, we identify Kibra as a member of the SWH network. Kibra, which colocalizes and associates with Mer and Ex, also promotes the Mer/Ex association. Furthermore, the Kibra/Mer association is conserved in human cells. Finally, Kibra complexes with Wts and kibra depletion in tissue culture cells induces a marked reduction in Yki phosphorylation without affecting the Yki/Wts interaction. We suggest that Kibra is part of an apical scaffold that promotes SWH pathway activity. ► The Salvador/Hippo/Warts network restricts tissue size ► We identify the scaffold protein Kibra as a SWH upstream regulator ► Kibra promotes SWH activity by complexing with multiple pathway members
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