Reactome | PDPK1 phosphorylates AKT at T308

PDPK1 phosphorylates AKT at T308

Stable Identifier

R-HSA-198270

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, plasma membrane

Locations in the PathwayBrowser

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Signal Transduction (Homo sapiens)

- Intracellular signaling by second messengers (Homo sapiens)
  - PIP3 activates AKT signaling (Homo sapiens)
    - PDPK1 phosphorylates AKT at T308 (Homo sapiens)
- Signaling by Receptor Tyrosine Kinases (Homo sapiens)
  - Signaling by VEGF (Homo sapiens)
    - VEGFA-VEGFR2 Pathway (Homo sapiens)
      - VEGFR2 mediated vascular permeability (Homo sapiens)
        
        PDPK1 phosphorylates AKT at T308 (Homo sapiens)

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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).

Literature References

PubMed ID	Title	Journal	Year
9736715	Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase kinase 3 and protein kinase B/AKT by the integrin-linked kinase Delcommenne, M, Tan, C, Gray, V, Rue, L, Woodgett, J, Dedhar, S	Proc Natl Acad Sci U S A	1998
7637810	Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction Burgering, BM, Coffer, PJ	Nature	1995