| Abstract: |
mTOR/RAFT1/FRAP is the target of the immunosuppressive drug rapamycin and the central component of a nutrient- and hormone-sensitive signaling pathway that regulates cell growth. We report that mTOR forms a stoichiometric complex with raptor, an evolutionarily conserved protein with at least two roles in the mTOR pathway. Raptor has a positive role in nutrient-stimulated signaling to the downstream effector S6K1, maintenance of cell size, and mTOR protein expression. The association of raptor with mTOR also negatively regulates the mTOR kinase activity. Conditions that repress the pathway, such as nutrient deprivation and mitochondrial uncoupling, stabilize the mTOR-raptor association and inhibit mTOR kinase activity. We propose that raptor is a missing component of the mTOR pathway that through its association with mTOR regulates cell size in response to nutrient levels. |
| Keywords: |
signal transduction; s6 kinase; controlled study; human tissue; protein expression; unclassified drug; human cell; nonhuman; proteins; cell division; enzyme inhibition; cell growth; protein kinases; protein protein interaction; protein; enzyme activity; evolution, molecular; regulatory mechanism; amino acid sequence; conserved sequence; molecular sequence data; nucleotide sequence; mammalian target of rapamycin; carrier proteins; adaptor proteins, signal transducing; cell line, transformed; phosphoproteins; cell size; protein structure, tertiary; binding sites; rapamycin; mitochondrion; sirolimus; food deprivation; culture media; stoichiometry; nutrient availability; repetitive sequences, amino acid; ribosomal protein s6 kinases; raptores; raptor; humans; human; priority journal; article; protein raptor
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