Apoptosis and Proliferation Control Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Dev Cell. 2010 Feb 16;18(2):300-8. doi: 10.1016/j.devcel.2009.12.011.
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.
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。
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