title: Rheb is an essential regulator of S6K in controlling cell growth in Drosophila.
abstract: 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).
authors.affiliation: Zoologisches Institut der Universität Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
authors.forename: Hugo
authors.initials: H
authors.lastname: Stocker
authors.forename: Thomas
authors.initials: T
authors.lastname: Radimerski
authors.forename: Benno
authors.initials: B
authors.lastname: Schindelholz
authors.forename: Franz
authors.initials: F
authors.lastname: Wittwer
authors.forename: Priyanka
authors.initials: P
authors.lastname: Belawat
authors.forename: Pierre
authors.initials: P
authors.lastname: Daram
authors.forename: Sebastian
authors.initials: S
authors.lastname: Breuer
authors.forename: George
authors.initials: G
authors.lastname: Thomas
authors.forename: Ernst
authors.initials: E
authors.lastname: Hafen
mesh_terms: D000818:Animals; D002455:Cell Division / Q000235:genetics* / Q000502:physiology; D048429:Cell Size / Q000235:genetics / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics; D005123:Eye / Q000648:ultrastructure; D005260:Female; D017353:Gene Deletion; D017344:Genes, Insect; D016147:Genes, Tumor Suppressor; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism*; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D009479:Neuropeptides / Q000235:genetics / Q000502:physiology*; D000076205:Ras Homolog Enriched in Brain Protein; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015533:Transcriptional Activation; D019076:Transgenes
chemical_list: D029721:Drosophila Proteins; D006133:Growth Substances; D009479:Neuropeptides; D000076205:Ras Homolog Enriched in Brain Protein; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C490212:Rheb protein, Drosophila; D019893:Ribosomal Protein S6 Kinases; D020559:Monomeric GTP-Binding Proteins