| 背景 | GTP-binding protein Rheb is a ~20 kDa protein. Small GTPase that acts as an allosteric activator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth. In response to nutrients, growth factors or amino acids, specifically activates the protein kinase activity of MTOR, the catalytic component of the mTORC1 complex: acts by causing a conformational change that allows the alignment of residues in the active site of MTOR, thereby enhancing the phosphorylation of ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1). RHEB is also required for localization of the TSC-TBC complex to lysosomal membranes. In response to starvation, RHEB is inactivated by the TSC-TBC complex, preventing activation of mTORC1. Has low intrinsic GTPase activity. 1. Inoki, K. et al. (2002) Nature cell biology 4, 648-57. PMID: 121725532. Tee, AR. et al. (2002) Proceedings of the National Academy of Sciences of the United States of America 99, 13571-6. PMID: 122711413. Castro, AF. et al. (2003) The Journal of biological chemistry 278, 32493-6. PMID: 128428884. Inoki, K. et al. (2003) Genes & development 17, 1829-34. PMID: 128695865. Tee, AR. et al. (2003) Current biology : CB 13, 1259-68. PMID: 129067856. Li, Y. et al. (2004) Molecular and cellular biology 24, 7965-75. PMID: 153400597. Long, X. et al. (2005) Current biology : CB 15, 702-13. PMID: 1585490210. Mazhab-Jafari, MT. et al. (2012) Structure (London, England : 1993) 20, 1528-39. PMID: 22819219 |
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