Rheb is an essential regulator of S6K in controlling cell growth in Drosophila

Nat Cell Biol. 2003 Jun;5(6):559-65. doi: 10.1038/ncb995.


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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Division / genetics*
  • Cell Division / physiology
  • Cell Size / genetics
  • Cell Size / physiology
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Eye / ultrastructure
  • Female
  • Gene Deletion
  • Genes, Insect
  • Genes, Tumor Suppressor
  • Growth Substances / genetics
  • Growth Substances / metabolism*
  • Monomeric GTP-Binding Proteins / genetics
  • Monomeric GTP-Binding Proteins / physiology*
  • Neuropeptides / genetics
  • Neuropeptides / physiology*
  • Ras Homolog Enriched in Brain Protein
  • Recombinant Fusion Proteins / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Ribosomal Protein S6 Kinases / genetics
  • Ribosomal Protein S6 Kinases / metabolism*
  • Signal Transduction
  • Transcriptional Activation
  • Transgenes


  • Drosophila Proteins
  • Growth Substances
  • Neuropeptides
  • Ras Homolog Enriched in Brain Protein
  • Recombinant Fusion Proteins
  • Repressor Proteins
  • Rheb protein, Drosophila
  • Ribosomal Protein S6 Kinases
  • Monomeric GTP-Binding Proteins