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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Apoptosis
  • Base Sequence
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / physiology*
  • Cell Proliferation
  • Drosophila / genetics
  • Drosophila / growth & development*
  • Drosophila / physiology*
  • Drosophila Proteins / antagonists & inhibitors
  • Drosophila Proteins / genetics
  • Drosophila Proteins / physiology*
  • Epistasis, Genetic
  • Female
  • Gene Expression Regulation, Developmental
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / physiology*
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology
  • Neurofibromin 2 / genetics
  • Neurofibromin 2 / physiology
  • Ovarian Follicle / cytology
  • Ovarian Follicle / physiology
  • Phenotype
  • Protein Kinases / genetics
  • Protein Kinases / physiology*
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / physiology*
  • RNA Interference
  • Signal Transduction
  • Tumor Suppressor Proteins / antagonists & inhibitors
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / physiology*

Substances

  • Cell Cycle Proteins
  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Neurofibromin 2
  • Tumor Suppressor Proteins
  • ex protein, Drosophila
  • kibra protein, Drosophila
  • merlin, Drosophila
  • sav protein, Drosophila
  • Protein Kinases
  • wts protein, Drosophila
  • Protein-Serine-Threonine Kinases
  • hpo protein, Drosophila