Raptor, a Binding Partner of Target of Rapamycin (TOR), Mediates TOR Action

• Published in: Cell 2002-07, Vol.110 (2), p.177-189
• Main Authors: Hara, Kenta, Maruki, Yoshiko, Long, Xiaomeng, Yoshino, Ken-ichi, Oshiro, Noriko, Hidayat, Sujuti, Tokunaga, Chiharu, Avruch, Joseph, Yonezawa, Kazuyoshi
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing; Animals; Base Sequence; Caenorhabditis elegans; Carrier Proteins - isolation & purification; Carrier Proteins - metabolism; Cell Line; Cloning, Molecular; DNA, Complementary; Enzyme Activation; Gene Expression; Gene Silencing; HeLa Cells; Humans; Molecular Sequence Data; Phenotype; Phosphoproteins - isolation & purification; Phosphoproteins - metabolism; Phosphorylation; Protein Binding; Protein Kinases - genetics; Protein Kinases - metabolism; Proteins - genetics; Proteins - isolation & purification; Proteins - metabolism; Regulatory-Associated Protein of mTOR; Ribosomal Protein S6 Kinases - metabolism; RNA Cap Analogs; RNA, Small Interfering; RNA, Untranslated; Sepharose; TOR Serine-Threonine Kinases
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(02)00833-4

mTOR controls cell growth, in part by regulating p70 S6 kinase α (p70α) and eukaryotic initiation factor 4E binding protein 1 (4EBP1). Raptor is a 150 kDa mTOR binding protein that also binds 4EBP1 and p70α. The binding of raptor to mTOR is necessary for the mTOR-catalyzed phosphorylation of 4EBP1 in vitro, and it strongly enhances the mTOR kinase activity toward p70α. Rapamycin or amino acid withdrawal increases, whereas insulin strongly inhibits, the recovery of 4EBP1 and raptor on 7-methyl-GTP Sepharose. Partial inhibition of raptor expression by RNA interference (RNAi) reduces mTOR-catalyzed 4EBP1 phosphorylation in vitro. RNAi of C. elegans raptor yields an array of phenotypes that closely resemble those produced by inactivation of Ce-TOR. Thus, raptor is an essential scaffold for the mTOR-catalyzed phosphorylation of 4EBP1 and mediates TOR action in vivo.