Protein: Target of rapamycin complex subunit LST8 (TORC subunit LST8) (G protein beta subunit-like) (Protein GbetaL) (Mammalian lethal with SEC13 protein 8) (mLST8) (Q9Z2K5)
Organism: Rattus norvegicus (Rat)
Function: Subunit of both mTORC1 and mTORC2, which regulates cell growth and survival in response to nutrient and hormonal signals. mTORC1 is activated in response to growth factors or amino acids. Growth factor-stimulated mTORC1 activation involves a AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. Amino acid-signaling to mTORC1 requires its relocalization to the lysosomes mediated by the Ragulator complex and the Rag GTPases. Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. mTORC1 phosphorylates EIF4EBP1 and releases it from inhibiting the elongation initiation factor 4E (eiF4E). mTORC1 phosphorylates and activates S6K1 at 'Thr-389', which then promotes protein synthesis by phosphorylating PDCD4 and targeting it for degradation. Within mTORC1, LST8 interacts directly with MTOR and enhances its kinase activity. In nutrient-poor conditions, stabilizes the MTOR-RPTOR interaction and favors RPTOR-mediated inhibition of MTOR activity. mTORC2 is also activated by growth factors, but seems to be nutrient-insensitive. mTORC2 seems to function upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors. mTORC2 promotes the serum-induced formation of stress-fibers or F-actin. mTORC2 plays a critical role in AKT1 'Ser-473' phosphorylation, which may facilitate the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDK1 which is a prerequisite for full activation. mTORC2 regulates the phosphorylation of SGK1 at 'Ser-421'. mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-657' (By similarity).
Subcellular location: Lysosome membrane {ECO:0000250|UniProtKB:Q9BVC4}. Cytoplasm {ECO:0000269|PubMed:11182770}. Note=Targeting to lysosomal membrane depends on amino acid availability: mTORC1 is recruited to lysosome membranes via interaction with GTP-bound form of RagA/RRAGA (or RagB/RRAGB) in complex with the GDP-bound form of RagC/RRAGC (or RagD/RRAGD), promoting its mTORC1 recruitment to the lysosomes. {ECO:0000250|UniProtKB:Q9BVC4}.
Interaction partners:
- RPTOR independent companion of MTOR, complex 2
- AKT1 substrate 1
- DEP domain-containing mTOR-interacting protein
- Target of rapamycin complex 2 subunit MAPKAP1
- Regulatory-associated protein of mTOR
- Serine/threonine-protein kinase mTOR
- Proline-rich protein 5
- TELO2-interacting protein 1 homolog
- GTP-binding protein Rheb
- Eukaryotic translation initiation factor 4E-binding protein 1
Sequence:
MNTTPGTVGSDPVILATAGYDHTVRFWQAHSGICTRTVQHQDSQVNALEITPDRSMIAATGYQHIRMYDLNSNNPNPIISYDGVSKNIASVGFHEDGRWMYTGGEDCTARIWDLRSRNLQCQRIFQVNAPINCVCLHPNQAELIVGDQSGTSHIWDLKTDHNEQLIPEPEFSITSAHIDPDASYMAAVNSAGNCFVWNLTGGIGDEVTQLIPKTKIPAHTRYALQCRFSPDSTLLATCSADQTCKIWRTSNFSLMTELSIKSSNPGESSRGWMWGCAFSGDSQYIVTASSDNLARLWCVETGEIKREYGGHQKAVVCLAFNDSVLG