PDPK1 phosphorylates AKT at T308

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).

一旦 AKT 定位于质膜上，其两个关键残基将被磷酸化，以实现其完全活化。这两个残基分别是催化域激活环内的苏氨酸（AKT1 中的 T308）和羧基末端非催化区域的疏水基序（HM）中的丝氨酸（AKT1 中的 S473）。PDPK1（PDK1）是激活环激酶；此激酶还可直接磷酸化 p70S6K。之前被称为 PDK2 的 HM 激酶已被鉴定为哺乳动物 TOR（雷帕霉素靶点；Sarbassov 等，2005 年），但还有其他多种激酶也能够在 S473 位点磷酸化 AKT。由 TORC2 复合物介导的 AKT 在 S473 位点的磷酸化是 PDPK1 介导的 AKT 苏氨酸 T308（Scheid 等，2002 年，Sarabassov 等，2005 年）磷酸化的先决条件。