The TOR signaling pathway regulates cell growth and metabolism in response to various nutrient signals by forming complexes with either rictor or raptor. To distinguish the physiological roles of the complexes formed by the two different TOR partners, we compared the in vivo functions of rictor and raptor in Drosophila. In rictor-null mutants, Akt-induced tissue hyperplasia was reduced and Akt-Ser-505 phosphorylation was decreased. Furthermore, FOXO-dependent apoptosis, which is inhibited by Akt, was augmented in the rictor-null background, indicating that rictor is essential for the Akt-FOXO signaling module. We found that neither S6K-dependent cell growth nor S6K-Thr-398 phosphorylation was affected in rictor-null mutants. However, the knockdown of another TOR binding partner, raptor, decreased S6K-Thr-398 phosphorylation and inhibited S6K-induced cell overgrowth. Collectively, our findings strongly support that the association of TOR with rictor or raptor plays pivotal roles in TOR-mediated cell apoptosis and growth control by differentially regulating Akt- and S6K-dependent signaling pathways, respectively. (c) 2007 Elsevier Inc. All rights reserved.