caa a22 4500 530098407 20181217030326.0 cr unu---uuuuu 181026e20140211xx s 000 0 eng 10.3929/ethz-b-000081022 doi 10.1038/srep04048 doi (ETHRESEARCH)oai:www.research-collection.ethz.ch:20.500.11850/81022 Src tyrosine kinase signaling antagonizes nuclear localization of FOXO and inhibits its transcription factor activity [Elektronische Daten] [Margret H. Bülow, Torsten R. Bülow, Michael Hoch, Michael J. Pankratz, Martin A. Jünger] Sci Rep Open access ethresearch Biochemical experiments in mammalian cells have linked Src family kinase activity to the insulin signaling pathway. To explore the physiological link between Src and a central insulin pathway effector, we investigated the effect of different Src signaling levels on the Drosophila transcription factor dFOXO in vivo. Ectopic activation of Src42A in the starved larval fatbody was sufficient to drive dFOXO out of the nucleus. When Src signaling levels were lowered by means of loss-of-function mutations or pharmacological inhibition, dFOXO localization was shifted to the nucleus in growing animals, and transcription of the dFOXO target genes d4E-BP and dInR was induced. dFOXO loss-of-function mutations rescued the induction of dFOXO target gene expression and the body size reduction of Src42A mutant larvae, establishing dFOXO as a critical downstream effector of Src signaling. Furthermore, we provide evidence that the regulation of FOXO transcription factors by Src is evolutionarily conserved in mammalian cells. Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported http://creativecommons.org/licenses/by-nc-nd/3.0 ethresearch Cancer genetics ethresearch Cancer models ethresearch Cell growth ethresearch Genetic interaction ethresearch Bülow Margret H. joint author Bülow Torsten R. joint author Hoch Michael joint author Pankratz Michael J. joint author Jünger Martin A. joint author Scientific Reports London : Nature Publishing Group 4, p. 4048 2045-2322 http://hdl.handle.net/20.500.11850/81022 text/html WWW-Backlink auf das Repository (Open access) 1 Journal Article ethresearch ETHRESEARCH 856 40 http://hdl.handle.net/20.500.11850/81022 text/html WWW-Backlink auf das Repository (Open access) ETHRESEARCH 700 1- Bülow Margret H. joint author ETHRESEARCH 700 1- Bülow Torsten R. joint author ETHRESEARCH 700 1- Hoch Michael joint author ETHRESEARCH 700 1- Pankratz Michael J. joint author ETHRESEARCH 700 1- Jünger Martin A. joint author ETHRESEARCH 773 0- Scientific Reports London : Nature Publishing Group 4, p. 4048 2045-2322 BK010053 XK010053 XK010000 ETHRESEARCH ETHRESEARCH ETHRESEARCH Journal Article Open access