naa a22 4500 528783572 20180924065515.0 cr unu---uuuuu 180924e20080116xx s 000 0 eng 10.3929/ethz-b-000013727 doi 10.1371/journal.pone.0001447 doi (ETHRESEARCH)oai:www.research-collection.ethz.ch:20.500.11850/13727 Drosophila cbl is essential for control of cell death and cell differentiation during eye development [Elektronische Daten] [Yuan Wang, Christian Werz, Dongbin Xu, Zhihong Chen, Ying Li, Ernst Hafen, Andreas Bergmann] PLoS ONE Open access ethresearch Background Activation of cell surface receptors transduces extracellular signals into cellular responses such as proliferation, differentiation and survival. However, as important as the activation of these receptors is their appropriate spatial and temporal down-regulation for normal development and tissue homeostasis. The Cbl family of E3-ubiquitin ligases plays a major role for the ligand-dependent inactivation of receptor tyrosine kinases (RTKs), most notably the Epidermal Growth Factor Receptor (EGFR) through ubiquitin-mediated endocytosis and lysosomal degradation. Methodology/Principal Findings Here, we report the mutant phenotypes of Drosophila cbl (D-cbl) during eye development. D-cbl mutants display overgrowth, inhibition of apoptosis, differentiation defects and increased ommatidial spacing. Using genetic interaction and molecular markers, we show that most of these phenotypes are caused by increased activity of the Drosophila EGFR. Our genetic data also indicate a critical role of ubiquitination for D-cbl function, consistent with biochemical models. Conclusions/Significance These data may provide a mechanistic model for the understanding of the oncogenic activity of mammalian cbl genes. Creative Commons Attribution 3.0 Unported http://creativecommons.org/licenses/by/3.0 ethresearch Wang Yuan joint author Werz Christian joint author Xu Dongbin joint author Chen Zhihong joint author Li Ying joint author Hafen Ernst joint author Bergmann Andreas joint author PLoS ONE Lawrence, Kan. : Public Library of Science 3 (1), pp. e1447-e1447 1932-6203 http://hdl.handle.net/20.500.11850/13727 text/html WWW-Backlink auf das Repository (Open access) 1 Journal Article ethresearch ETHRESEARCH 856 40 http://hdl.handle.net/20.500.11850/13727 text/html WWW-Backlink auf das Repository (Open access) ETHRESEARCH 700 1- Wang Yuan joint author ETHRESEARCH 700 1- Werz Christian joint author ETHRESEARCH 700 1- Xu Dongbin joint author ETHRESEARCH 700 1- Chen Zhihong joint author ETHRESEARCH 700 1- Li Ying joint author ETHRESEARCH 700 1- Hafen Ernst joint author ETHRESEARCH 700 1- Bergmann Andreas joint author ETHRESEARCH 773 0- PLoS ONE Lawrence, Kan. : Public Library of Science 3 (1), pp. e1447-e1447 1932-6203 BK010053 XK010053 XK010000 ETHRESEARCH ETHRESEARCH ETHRESEARCH Journal Article Open access