Kibra is a regulator of the Salvador/Warts/Hippo signaling network.
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.
Apoptosis and Proliferation Control Laboratory, Cancer Research UK, London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.
Alice
A
Genevet
Michael C
MC
Wehr
Ruth
R
Brain
Barry J
BJ
Thompson
Nicolas
N
Tapon
D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation; D004330:Drosophila / Q000235:genetics / Q000254:growth & development* / Q000502:physiology*; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D004843:Epistasis, Genetic; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D025581:Neurofibromin 2 / Q000235:genetics / Q000502:physiology; D006080:Ovarian Follicle / Q000166:cytology / Q000502:physiology; D010641:Phenotype; D011494:Protein Kinases / Q000235:genetics / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D000099317:Hippo Kinases
D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D025581:Neurofibromin 2; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D025521:Tumor Suppressor Proteins; C085090:ex protein, Drosophila; C548168:kibra protein, Drosophila; C099885:merlin, Drosophila; C465504:sav protein, Drosophila; C093503:wts protein, Drosophila; C499474:hpo protein, Drosophila; D000099317:Hippo Kinases