Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action.
mTOR controls cell growth, in part by regulating p70 S6 kinase alpha (p70alpha) and eukaryotic initiation factor 4E binding protein 1 (4EBP1). Raptor is a 150 kDa mTOR binding protein that also binds 4EBP1 and p70alpha. 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 p70alpha. 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.
Hara
Kenta
K
Biosignal Research Center, Kobe University, 657-8501, Kobe, Japan. harak@kobe-u.ac.jp
Maruki
Yoshiko
Y
Long
Xiaomeng
X
Yoshino
Ken-ichi
K
Oshiro
Noriko
N
Hidayat
Sujuti
S
Tokunaga
Chiharu
C
Avruch
Joseph
J
Yonezawa
Kazuyoshi
K
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans; D002352:Carrier Proteins / Q000302:isolation & purification / Q000378:metabolism; D018797:Cell Cycle Proteins; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004789:Enzyme Activation; D015870:Gene Expression; D020868:Gene Silencing; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D010641:Phenotype; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D012314:RNA Cap Analogs; D034741:RNA, Small Interfering; D022661:RNA, Untranslated; D000076223:Regulatory-Associated Protein of mTOR; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D012685:Sepharose; D058570:TOR Serine-Threonine Kinases
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D018076:DNA, Complementary; C087000:EIF4EBP1 protein, human; D010750:Phosphoproteins; D011506:Proteins; D012314:RNA Cap Analogs; D034741:RNA, Small Interfering; D022661:RNA, Untranslated; C463659:RPTOR protein, human; D000076223:Regulatory-Associated Protein of mTOR; C017516:7-methylguanosine triphosphate; D012685:Sepharose; D011494:Protein Kinases; C546842:MTOR protein, human; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases