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Protein Page:
LST8 (human)

LST8 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-422'. mTORC2 also modulates the phosphorylation of PRKCA on 'Ser-657'. Part of the mammalian target of rapamycin complex 1 (mTORC1) which contains MTOR, MLST8, RPTOR, AKT1S1/PRAS40 and DEPTOR. mTORC1 binds to and is inhibited by FKBP12-rapamycin. Part of the mammalian target of rapamycin complex 2 (mTORC2) which contains MTOR, MLST8, PRR5, RICTOR, MAPKAP1 and DEPTOR. Contrary to mTORC1, mTORC2 does not bind to and is not sensitive to FKBP12- rapamycin. Interacts directly with MTOR and RPTOR. Interacts with RHEB. Broadly expressed, with highest levels in skeletal muscle, heart and kidney. Belongs to the WD repeat LST8 family. 3 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: Autophagy
Chromosomal Location of Human Ortholog: 16p13.3
Cellular Component: cytoplasm; cytosol; nucleoplasm; TORC2 complex
Molecular Function: protein binding
Biological Process: cell cycle arrest; macroautophagy; phosphoinositide-mediated signaling; positive regulation of TOR signaling pathway; regulation of actin cytoskeleton organization and biogenesis; T cell costimulation
Reference #:  Q9BVC4 (UniProtKB)
Alt. Names/Synonyms: G protein beta subunit like; G protein beta subunit-like; Gable; GbetaL; GBL; LST8; Mammalian lethal with SEC13 protein 8; MGC111011; MLST8; MTOR associated protein, LST8 homolog (S. cerevisiae); POP3; Protein GbetaL; Target of rapamycin complex subunit LST8; TORC subunit LST8; WAT1
Gene Symbols: MLST8
Molecular weight: 35,876 Da
Basal Isoelectric point: 5.5  Predict pI for various phosphorylation states
CST Pathways:  AMPK Signaling  |  Autophagy Signaling  |  Insulin Receptor Signaling  |  mTOR Signaling  |  PI3K/Akt Signaling  |  T Cell Receptor Signaling  |  Translation: eIF4E and p70S6K
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