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

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

Disease (Homo sapiens)

- Infectious disease (Homo sapiens)
  - Viral Infection Pathways (Homo sapiens)
    - SARS-CoV Infections (Homo sapiens)
      - SARS-CoV-2 Infection (Homo sapiens)
        
        SARS-CoV-2-host interactions (Homo sapiens)
        
        SARS-CoV-2 targets host intracellular signalling and regulatory pathways (Homo sapiens)
        
        PDPK1 phosphorylates AKT at T308 (Homo sapiens)

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)

General

SBML | | PDF

SVG | | PPTX | SBGN

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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
7637810	Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction Burgering, BM, Coffer, PJ	Nature	1995
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

Participants

Input

Output

Participates

as an event of

Catalyst Activity

protein serine/threonine kinase activity of p-S-AKT:PDPK1:PIP3 [plasma membrane]

Physical Entity

p-S-AKT:PDPK1:PIP3 [plasma membrane] (Homo sapiens)

Activity

protein serine/threonine kinase activity (GO:0004674)

This event is regulated

Negatively by

Regulator

N:M:PDPK1 [plasma membrane] (Homo sapiens)

Active Unit

M [plasma membrane]

Authored

Nasi, S (2006-10-10)

Annibali, D (2006-10-10)

Reviewed

Greene, LA (2007-11-08)

Thorpe, L (2012-08-13)

Yuzugullu, H (2012-08-13)

Zhao, JJ (2012-08-13)

Messina, F (2022-02-18)

Created