FK506-binding protein 12-rapamycin complex-associated protein 1 ; FKBP12-rapamycin complex-associated protein ; Mammalian target of rapamycin ; mTOR ; Mechanistic target of rapamycin ; Rapamycin and FKBP12 target 1 ; Rapamycin target protein 1 ; FRAP ; FRAP1 ; FRAP2 ; RAFT1 ; RAPT1
Categories
Elisa
Function
Kinase 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 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-421', which then promotes protein synthesis by phosphorylating PDCD4 and targeting it for degradation. Phosphorylates MAF1 leading to attenuation of its RNA polymerase III-repressive function. 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'. Under nutrient sufficiency, phosphorylates ULK1 at 'Ser-757', disrupting the interaction with AMPK and preventing activation of ULK1.
Specificity
Natural and recombinant Human Serine/threonine-protein kinase mTOR
Subcellular Location
Endoplasmic reticulum membrane Peripheral membrane protein Cytoplasmic side Golgi apparatus membrane Peripheral membrane protein Cytoplasmic side Mitochondrion outer membrane Peripheral membrane protein Cytoplasmic side Lysosome Cytoplasm Nucleus PML body Shuttles between cytoplasm and nucleus. Accumulates in the nucleus in response to hypoxia (By similarity). Targeting to lysosomes depends on amino acid availability and RRAGA and RRAGB.
Interacts with PPAPDC3 and PML (By similarity). Part of the mammalian target of rapamycin complex 1 (mTORC1) which contains MTOR/FRAP1, MLST8, RPTOR and AKT1S1. mTORC1 binds to and is inhibited by FKBP12-rapamycin. Part of the mammalian target of rapamycin complex 2 (mTORC2) which contains MTOR, MLST8, PROTOR1, RICTOR and MAPKAP1. Contrary to mTORC1, mTORC2 does not bind to and is not sensitive to FKBP12-rapamycin. Binds directly to PROTOR1 and RICTOR within the mTORC2 complex. Interacts with UBQLN1. Interacts with DEPTOR. Interacts with TTI1 and TELO2.