Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins.
Mutations in the TSC1 or TSC2 genes cause tuberous sclerosis, a benign tumour syndrome in humans. Tsc2 possesses a domain that shares homology with the GTPase-activating protein (GAP) domain of Rap1-GAP, suggesting that a GTPase might be the physiological target of Tsc2. Here we show that the small GTPase Rheb ... (Ras homologue enriched in brain) is a direct target of Tsc2 GAP activity both in vivo and in vitro. Point mutations in the GAP domain of Tsc2 disrupted its ability to regulate Rheb without affecting the ability of Tsc2 to form a complex with Tsc1. Our studies identify Rheb as a molecular target of the TSC tumour suppressors.
Mesh Terms:
1-Phosphatidylinositol 3-Kinase, Animals, Drosophila Proteins, Drosophila melanogaster, GTP-Binding Proteins, GTPase-Activating Proteins, Gene Expression Regulation, Fungal, Genes, Suppressor, Glutathione Transferase, Monomeric GTP-Binding Proteins, Neuropeptides, Point Mutation, Proteins, Recombinant Fusion Proteins, Repressor Proteins, Ribosomal Protein S6 Kinases, Tuberous Sclerosis, Tumor Suppressor Proteins
1-Phosphatidylinositol 3-Kinase, Animals, Drosophila Proteins, Drosophila melanogaster, GTP-Binding Proteins, GTPase-Activating Proteins, Gene Expression Regulation, Fungal, Genes, Suppressor, Glutathione Transferase, Monomeric GTP-Binding Proteins, Neuropeptides, Point Mutation, Proteins, Recombinant Fusion Proteins, Repressor Proteins, Ribosomal Protein S6 Kinases, Tuberous Sclerosis, Tumor Suppressor Proteins
Nat. Cell Biol.
Date: Jun. 01, 2003
PubMed ID: 12771962
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