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Kibra 是 Salvador/Warts/Hippo 信号通路的调节因子。

Kibra is a regulator of the Salvador/Warts/Hippo signaling network.

机构信息

Apoptosis and Proliferation Control Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.

出版信息

Dev Cell. 2010 Feb 16;18(2):300-8. doi: 10.1016/j.devcel.2009.12.011.

Abstract

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.

摘要

Salvador(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。该途径的核心由 MST 和 LATS 家族激酶级联组成,最终磷酸化并使 YAP/Yorkie(Yki)转录共激活因子失活。FERM 结构域蛋白 Merlin(Mer)和 Expanded(Ex)代表一种控制途径活性的上游调节模式。在这里,我们将 Kibra 鉴定为 SWH 网络的成员。Kibra 与 Mer 和 Ex 共定位并相互作用,也促进了 Mer/Ex 相互作用。此外,Kibra 与 Mer 的结合在人类细胞中是保守的。最后,在组织培养细胞中,Kibra 复合物与 Wts 一起被耗尽,导致 Yki 磷酸化显著减少,而不影响 Yki/Wts 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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2995/2845807/ac6a895c1c36/gr1.jpg

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