Insulin signalling is a potent stimulator of cell growth and has been proposed 
to function, at least in part, through the conserved protein kinase TOR (target 
of rapamycin) [corrected]. Recent studies suggest that the tuberous sclerosis 
complex Tsc1-Tsc2 may couple insulin signalling to Tor activity [corrected]. 
However, the regulatory mechanism involved remains unclear, and additional 
components are most probably involved. In a screen for novel regulators of 
growth, we identified Rheb (Ras homologue enriched in brain), a member of the 
Ras superfamily of GTP-binding proteins. Increased levels of Rheb in Drosophila 
melanogaster promote cell growth and alter cell cycle kinetics in multiple 
tissues. In mitotic tissues, overexpression of Rheb accelerates passage through 
G1-S phase without affecting rates of cell division, whereas in endoreplicating 
tissues, Rheb increases DNA ploidy. Mutation of Rheb suspends larval growth and 
prevents progression from first to second instar. Genetic and biochemical tests 
indicate that Rheb functions in the insulin signalling pathway downstream of 
Tsc1-Tsc2 and upstream of TOR. Levels of rheb mRNA are rapidly induced in 
response to protein starvation, and overexpressed Rheb can drive cell growth in 
starved animals, suggesting a role for Rheb in the nutritional control of cell 
growth.