Abstract
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
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Division / genetics*
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Cell Division / physiology
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Cell Size / genetics
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Cell Size / physiology
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism*
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Drosophila melanogaster / genetics
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Eye / ultrastructure
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Female
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Gene Deletion
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Genes, Insect
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Genes, Tumor Suppressor
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Growth Substances / genetics
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Growth Substances / metabolism*
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Monomeric GTP-Binding Proteins / genetics
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Monomeric GTP-Binding Proteins / physiology*
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Neuropeptides / genetics
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Neuropeptides / physiology*
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Ras Homolog Enriched in Brain Protein
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Recombinant Fusion Proteins / metabolism
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Repressor Proteins / genetics
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Repressor Proteins / metabolism
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Ribosomal Protein S6 Kinases / genetics
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Ribosomal Protein S6 Kinases / metabolism*
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Signal Transduction
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Transcriptional Activation
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Transgenes
Substances
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Drosophila Proteins
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Growth Substances
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Neuropeptides
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Ras Homolog Enriched in Brain Protein
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Recombinant Fusion Proteins
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Repressor Proteins
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Rheb protein, Drosophila
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Ribosomal Protein S6 Kinases
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Monomeric GTP-Binding Proteins