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http://purl.uniprot.org/citations/15066126http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/15066126http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/15066126http://www.w3.org/2000/01/rdf-schema#comment"The mammalian target of rapamycin (mTOR) is a Ser/Thr protein kinase that plays a crucial role in a nutrient-sensitive signalling pathway that regulates cell growth. TOR signalling is potently inhibited by rapamycin, through the direct binding of a FK506-binding protein 12 (FKBP12)/rapamycin complex to the TOR FRB domain, a segment amino terminal to the kinase catalytic domain. The molecular basis for the inhibitory action of FKBP12/rapamycin remains uncertain. Raptor (regulatory associated protein of mTOR) is a recently identified mTOR binding partner that is essential for mTOR signalling in vivo, and whose binding to mTOR is critical for mTOR-catalysed substrate phosphorylation in vitro. Here we investigated the stability of endogenous mTOR/raptor complex in response to rapamycin in vivo, and to the direct addition of a FKBP12/rapamycin complex in vitro. Rapamycin diminished the recovery of endogenous raptor with endogenous or recombinant mTOR in vivo; this inhibition required the ability of mTOR to bind the FKBP12/rapamycin complex, but was independent of mTOR kinase activity. Rapamycin, in the presence of FKBP12, inhibited the association of raptor with mTOR directly in vitro, and concomitantly reduced the mTOR-catalysed phosphorylation of raptor-dependent, but not raptor-independent substrates; mTOR autophosphorylation was unaltered. These observations indicate that rapamycin inhibits mTOR function, at least in part, by inhibiting the interaction of raptor with mTOR; this action uncouples mTOR from its substrates, and inhibits mTOR signalling without altering mTOR's intrinsic catalytic activity."xsd:string
http://purl.uniprot.org/citations/15066126http://purl.org/dc/terms/identifier"doi:10.1111/j.1356-9597.2004.00727.x"xsd:string
http://purl.uniprot.org/citations/15066126http://purl.org/dc/terms/identifier"doi:10.1111/j.1356-9597.2004.00727.x"xsd:string
http://purl.uniprot.org/citations/15066126http://purl.uniprot.org/core/author"Hara K."xsd:string
http://purl.uniprot.org/citations/15066126http://purl.uniprot.org/core/author"Hara K."xsd:string
http://purl.uniprot.org/citations/15066126http://purl.uniprot.org/core/author"Tokunaga C."xsd:string
http://purl.uniprot.org/citations/15066126http://purl.uniprot.org/core/author"Tokunaga C."xsd:string
http://purl.uniprot.org/citations/15066126http://purl.uniprot.org/core/author"Yonezawa K."xsd:string
http://purl.uniprot.org/citations/15066126http://purl.uniprot.org/core/author"Yonezawa K."xsd:string
http://purl.uniprot.org/citations/15066126http://purl.uniprot.org/core/author"Yoshino K."xsd:string
http://purl.uniprot.org/citations/15066126http://purl.uniprot.org/core/author"Yoshino K."xsd:string
http://purl.uniprot.org/citations/15066126http://purl.uniprot.org/core/author"Avruch J."xsd:string
http://purl.uniprot.org/citations/15066126http://purl.uniprot.org/core/author"Avruch J."xsd:string
http://purl.uniprot.org/citations/15066126http://purl.uniprot.org/core/author"Hidayat S."xsd:string
http://purl.uniprot.org/citations/15066126http://purl.uniprot.org/core/author"Hidayat S."xsd:string
http://purl.uniprot.org/citations/15066126http://purl.uniprot.org/core/author"Oshiro N."xsd:string
http://purl.uniprot.org/citations/15066126http://purl.uniprot.org/core/author"Oshiro N."xsd:string
http://purl.uniprot.org/citations/15066126http://purl.uniprot.org/core/author"Eguchi S."xsd:string
http://purl.uniprot.org/citations/15066126http://purl.uniprot.org/core/author"Eguchi S."xsd:string
http://purl.uniprot.org/citations/15066126http://purl.uniprot.org/core/date"2004"xsd:gYear
http://purl.uniprot.org/citations/15066126http://purl.uniprot.org/core/date"2004"xsd:gYear
http://purl.uniprot.org/citations/15066126http://purl.uniprot.org/core/name"Genes Cells"xsd:string
http://purl.uniprot.org/citations/15066126http://purl.uniprot.org/core/name"Genes Cells"xsd:string