Rheb promotes cell growth as a component of the insulin/TOR signalling network

Leslie J. Saucedo, Xinsheng Gao, Dominic A. Chiarelli, Ling Li, Duoija Pan, Bruce A. Edgar

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Abstract

Insulin signalling is a potent inhibitor of cell growth and has been proposed to function, at least in part, through the conserved protein kinase TOR (target of rapamycin). Recent studies suggest a that the tuberous sclerosis complex Tsc1-Tsc2 may couple insulin signalling to Tor activity. 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.

Original languageEnglish (US)
Pages (from-to)566-571
Number of pages6
JournalNature Cell Biology
Volume5
Issue number6
DOIs
Publication statusPublished - Jun 1 2003

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ASJC Scopus subject areas

  • Cell Biology

Cite this

Saucedo, L. J., Gao, X., Chiarelli, D. A., Li, L., Pan, D., & Edgar, B. A. (2003). Rheb promotes cell growth as a component of the insulin/TOR signalling network. Nature Cell Biology, 5(6), 566-571. https://doi.org/10.1038/ncb996