RICTOR

Component of the mechanistic target of rapamycin complex 2 (mTORC2), which transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organisation, lipogenesis and anabolic output. In response to growth factors, mTORC2 phosphorylates and activates AGC protein kinase family members, including AKT (AKT1, AKT2 and AKT3), PKC (PRKCA, PRKCB and PRKCE) and SGK1. In contrast to mTORC1, mTORC2 is nutrient-insensitive. Within the mTORC2 complex, RICTOR probably acts as a molecular adapter. RICTOR is responsible for the FKBP12-rapamycin-insensitivity of mTORC2. mTORC2 plays a critical role in AKT1 activation by mediating phosphorylation of different sites depending on the context, such as 'Thr-450', 'Ser-473', 'Ser-477' or 'Thr-479', facilitating the phosphorylation of the activation loop of AKT1 on 'Thr-308' by PDPK1/PDK1 which is a prerequisite for full activation. mTORC2 catalyses the phosphorylation of SGK1 at 'Ser-422' and of PRKCA on 'Ser-657'. The mTORC2 complex also phosphorylates various proteins involved in insulin signalling, such as FBXW8 and IGF2BP1. mTORC2 acts upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors. mTORC2 promotes the serum-induced formation of stress-fibres or F-actin. Location: Cell membrane; Endoplasmic reticulum membrane; Lysosome membrane (UniProt). Locus 5p13.1 (HGNC).