Rheb is an essential regulator of S6K in controlling cell growth in Drosophila.
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).
Stocker
Hugo
H
Zoologisches Institut der Universität Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
Radimerski
Thomas
T
Schindelholz
Benno
B
Wittwer
Franz
F
Belawat
Priyanka
P
Daram
Pierre
P
Breuer
Sebastian
S
Thomas
George
G
Hafen
Ernst
E
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
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