Project Overview: Organ size is strictly regulated by various signalling pathways, which control organ size either by modulating cell size or by cell number. The Hippo (Hpo) pathway is a major input controlling cell number during development and disease; it restricts tissue growth by promoting apoptosis and by inhibiting cell. Once activated by an as yet unknown mechanism, Hpo phosphorylates the scaffold proteins Sav and Mats, as well as Wts. This leads to Wts activation, and phosphorylation by Wts of its binding partner, the transcriptional co-activator Yki. When Yki is phosphorylated by Wts it is inactive, leading to a reduction in cell number owing to downregulation of its transcriptional targets, the anti-apoptotic molecules DIAP1 and ban, and the cell cycle regulator cyclin E. The Hpo pathway has been implicated in tumour suppression in mammals.Using a new approach to analyse protein-protein interactions termed split-TEV, we will seek to identify new upstream members of the Hpo pathway, as well as study the dynamics of pathway activation in vivo. Since split-TEV was optimized for its application in mammalian cells, initial experiments included the adaptation of the technique to Drosophila cell culture, and the testing of known interactions such as the association of Yorkie (Yki) with 14-3-3 proteins, and the interaction between Hpo and its partners, Salvador and dRASSF 
Screener: Michael Wehr (Tapon Lab).
Extension:3661, Rm 230
Project Status: Published
Publications: Salt-inducible kinases regulate growth through the Hippo signalling pathway in Drosophila.. Wehr et al., 2012
Project Start Date: Sep 2008
Keywords: Hippo signalling
Libraries Screened:
  •   Ambion Genome Library