Rictor is a novel target of p70 S6 kinase-1.
The rapamycin-insensitive companion of mammalian target of rapamycin (mTOR) (Rictor) is a key member of mTOR complex-2 (mTORC2), which phosphorylates the AGC kinases Akt/PKB, PKC and SGK1 at a C-terminal hydrophobic motif. We identified several novel sites on Rictor that are phosphorylated, including Thr1135, which is conserved across all vertebrates. Phosphorylation of this site on Rictor is stimulated by amino acids and growth factors through a rapamycin-sensitive signaling cascade. We demonstrate here that Rictor is a direct target of the ribosomal protein S6 kinase-1 (S6K1). Rictor phosphorylation at Thr1135 does not lead to major changes in mTORC2-kinase activity. However, phosphorylation of this site turns over rapidly and mediates 14-3-3 binding to Rictor and mTORC2, providing possibility for altered interactions of the complex. These findings reveal an unexpected signaling input into mTORC2, which is regulated by amino acids, growth factors and rapamycin.
Treins
C
C
Signal Transduction Laboratory, Cancer Research UK London Research Institute, London, UK.
Warne
P H
PH
Magnuson
M A
MA
Pende
M
M
Downward
J
J
D048948:14-3-3 Proteins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D051381:Rats; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism*; D013912:Threonine; D014157:Transcription Factors / Q000378:metabolism
D048948:14-3-3 Proteins; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D014157:Transcription Factors; C550254:rictor protein, rat; D013912:Threonine; D038762:Ribosomal Protein S6 Kinases, 70-kDa