TORC2 (mTOR) phosphorylates AKT at S473

Stable Identifier
R-HSA-198640
Type
Reaction [transition]
Species
Homo sapiens
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Under conditions of growth and mitogen stimulation S473 phosphorylation of AKT is carried out by mTOR (mammalian Target of Rapamycin). This kinase is found in two structurally and functionally distinct protein complexes, named TOR complex 1 (TORC1) and TOR complex 2 (TORC2). It is TORC2 complex, which is composed of mTOR, RICTOR, SIN1 (also named MAPKAP1) and LST8, that phosphorylates AKT at S473 (Sarbassov et al., 2005). This complex also regulates actin cytoskeletal reorganization (Jacinto et al., 2004; Sarbassov et al., 2004). TORC1, on the other hand, is a major regulator of ribosomal biogenesis and protein synthesis (Hay and Sonenberg, 2004). TORC1 regulates these processes largely by the phosphorylation/inactivation of the repressors of mRNA translation 4E binding proteins (4E BPs) and by the phosphorylation/activation of ribosomal S6 kinase (S6K1). TORC1 is also the principal regulator of autophagy. In other physiological conditions, other kinases may be responsible for AKT S473 phosphorylation.
Phosphorylation of AKT on S473 by TORC2 complex is a prerequisite for AKT phosphorylation on T308 by PDPK1 (Scheid et al. 2002, Sarabassov et al. 2005).

Literature References
PubMed ID Title Journal Year
12167717 Multiple phosphoinositide 3-kinase-dependent steps in activation of protein kinase B

Scheid, MP, Marignani, PA, Woodgett, JR

Mol Cell Biol 2002
15718470 Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex

Sarbassov, DD, Guertin, DA, Ali, SM, Sabatini, DM

Science 2005
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Title
protein serine/threonine kinase activity of TORC2 complex [cytosol]
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