Article

Kibra Is a Regulator of the Salvador/Warts/Hippo Signaling Network

Apoptosis and Proliferation Control Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Developmental Cell (Impact Factor: 9.71). 02/2010; 18(2):300-8. DOI: 10.1016/j.devcel.2009.12.011
Source: PubMed

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.

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Available from: Michael C Wehr, Oct 23, 2014
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    • "Models of spatial regulation of LATS1/2 kinase activities were proposed a long time ago and have been further refined in the last few years. Early studies have shown that Hpo/Sav interact with Mer/Ex and that Wts associates with Kibra (Genevet et al. 2010; Yu et al. 2010). This interaction suggests that the Mer/Ex/Kibra complex may recruit Hpo and Wts to the apical plasma membrane and results in Wts phosphorylation by Hpo. "
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    • "The effect of Kibra varies in different tissue types. Loss of Kibra leads to accumulation of aPKC in the Drosophila posterior follicle cells[12]. After confirming that aPKC binds to Kibra in vitro, we examined the genetic interaction between Kibra and aPKC in regulating autophagy in the larval fat body. "
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    • " ( 1 : 200 , Z378B , Promega ) , rabbit anti - β - galactosidase ( 1 : 1000 , 55976 , Cappel ) , rabbit anti - activated caspase 3 ( 1 : 150 , 9661L , Cell Signaling ) , rat anti - DE - Cad ( 1 : 50 , CAD2 , DSHB ) , rabbit anti - Ex ( 1 : 200 , a gift from A . Laughon , University of Wisconsin , Madison , WI , USA ) and rat anti - Yki ( 1 : 200 , Genevet et al . , 2010 ) . Rhodamine - conjugated phalloidin ( Sigma ) was used at a concentration of 0 . 3 μM . Fluorescently labeled secondary antibodies were from Jackson Immunoresearch ( 1 : 200 ) ."
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