Meta-Biol

• Pathways

Once AKT is localized at the plasma membrane, it is phosphorylated at two critical residues for its full activation. These residues are a threonine (T308 in AKT1) in the activation loop within the catalytic domain, and a serine (S473 in AKT1), in a hydrophobic motif (HM) within the carboxy terminal, non-catalytic region. PDPK1 (PDK1) is the activation loop kinase; this kinase can also directly phosphorylate p70S6K. The HM kinase, previously termed PDK2, has been identified as the mammalian TOR (Target Of Rapamycin; Sarbassov et al., 2005) but several other kinases are also able to phosphorylate AKT at S473. Phosphorylation of AKT at S473 by TORC2 complex is a prerequisite for PDPK1-mediated phosphorylation of AKT threonine T308 (Scheid et al. 2002, Sarabassov et al. 2005).