Rheb is an essential regulator of S6K in controlling cell growth in Drosophila

• Published in: Nature cell biology Vol. 5; no. 6; pp. 559 - 566
• Main Authors: Hafen, Ernst, Stocker, Hugo, Radimerski, Thomas, Schindelholz, Benno, Wittwer, Franz, Belawat, Priyanka, Daram, Pierre, Breuer, Sebastian, Thomas, George
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.06.2003
• Subjects: Animals; Cell Division - genetics; Cell Division - physiology; Cell growth; Cell Size - genetics; Cell Size - physiology; Cellular control mechanisms; Cloning; Drosophila; Drosophila melanogaster; Drosophila melanogaster - genetics; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Exocrine glands; Eye - ultrastructure; Female; Gene Deletion; Genes; Genes, Insect; Genes, Tumor Suppressor; Genetic aspects; Genotype & phenotype; Growth Substances - genetics; Growth Substances - metabolism; Insects; Kinases; Monomeric GTP-Binding Proteins - genetics; Monomeric GTP-Binding Proteins - physiology; Mutation; Neuropeptides - genetics; Neuropeptides - physiology; Ovaries; Physiological aspects; Ras Homolog Enriched in Brain Protein; Recombinant Fusion Proteins - metabolism; Repressor Proteins - genetics; Repressor Proteins - metabolism; Ribosomal Protein S6 Kinases - genetics; Ribosomal Protein S6 Kinases - metabolism; Signal Transduction; Transcriptional Activation; Transgenes; Tumor suppressor genes; Switzerland
• ISSN: 1465-7392; 1476-4679; 1476-4679
• DOI: 10.1038/ncb995

Understanding the mechanisms through which multicellular organisms regulate cell, organ and body growth is of relevance to developmental biology and to research on growth-related diseases such as cancer. Here we describe a new effector in growth control, the small GTPase Rheb (Ras homologue enriched in brain). Mutations in the Drosophila melanogaster Rheb gene were isolated as growth-inhibitors, whereas overexpression of Rheb promoted cell growth. Our genetic and biochemical analyses suggest that Rheb functions downstream of the tumour suppressors Tsc1 (tuberous sclerosis 1)-Tsc2 in the TOR (target of rapamycin) signalling pathway to control growth, and that a major effector of Rheb function is ribosomal S6 kinase (S6K).