A misexpression screen for negative regulators of PI3K/PKB signaling. F. Wittwer 1, P. Wuestemann 1, W. Brogiolo 1, H. Stocker 1, D. Nellen 2, K. Basler 2, E. Hafen 1. 1) Zoologisches Institut der Universitaet Zuerich, Winterthurerstrasse 190, CH-8057 Zuerich, Switzerland; 2) Institut fuer Molekularbiologie der Universitaet Zuerich, Winterthurerstrasse 190, CH-8057 Zuerich, Switzerland.
The PI3K/PKB signaling cascade regulates growth and metabolism and has been conserved during evolution. It is assumed that several negative regulators of this cascade in mammals and Drosophila have not been identified yet. We therefore screened for genes, which upon overexpression suppress growth phenotypes resulting from overactivation of PI3K/PKB signaling in the eye of Drosophila. Among the genes identified in this screen are those, encoding the protein tyrosine phosphatases dMEG1 and Ptp99A. These phosphatases may inhibit dINR or Chico/dIRS, which are key components of PI3K/PKB signaling. dMEG1 reduces organ size by suppressing cell number and cell size, which is compatible with a function in PKB/PI3K signaling. This screen identifies several additional negative regulators of growth, which have not been implicated in PI3K/PKB signaling yet. Some of them have no or only a weak loss-of-function phenotype and therefore have not been isolated in previous screens, which were based on selecting for such phenotypes.