Disease relevance of RICTOR

• Signaling mediated by the mammalian target of rapamycin kinase (mTOR) is activated during human cytomegalovirus (HCMV) infection. mTOR is found in two complexes differing by the binding partner, rictor or raptor [1].

High impact information on RICTOR

• Disruption of the Rictor gene in mice results in embryonic lethality and ablates Akt phosphorylation [2].
• The distinct complex of mTOR, mLST8, and rictor (mTORC2) does not interact with FKBP12-rapamycin and is not thought to be rapamycin sensitive. mTORC2 phosphorylates and activates Akt/PKB, a key regulator of cell survival [3].
• Surprisingly, the inhibitory effects of rapamycin on viral growth are primarily due to the presence of rictor, not raptor [1].
• Human cytomegalovirus infection alters the substrate specificities and rapamycin sensitivities of raptor- and rictor-containing complexes [1].

Biological context of RICTOR

• Here we show that HCMV infection also activates the rictor complex, as indicated by increased phosphorylation of Akt S473; this phosphorylation is insensitive to rapamycin but sensitive to caffeine in both uninfected and infected cells [1].
• These data suggest that, during HCMV infection, the rictor- and raptor-containing complexes are modified such that their substrate specificities and rapamycin sensitivities are altered [1].
• Downregulation of raptor or rictor by RNA interference (RNAi) decreased cell motility [4].

References