Nature Cell Biology5, 559 - 566 (2003)
Published online: 27 May 2003; | doi:10.1038/ncb995
Rheb is an essential regulator of S6K in controlling cell growth in Drosophila
Hugo Stocker1, Thomas Radimerski2, Benno Schindelholz3, Franz Wittwer1, Priyanka Belawat1, Pierre Daram3, Sebastian Breuer3, George Thomas2
& Ernst Hafen1
1
Zoologisches Institut der Universität Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland.
2
Friedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
3
The Genetics Company, Inc., Wagistrasse 27, 8952 Zürich-Schlieren, Switzerland.
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).
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