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

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        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)
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        PDPK1 phosphorylates AKT at T308 (Homo sapiens)

General

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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 Rue, L, Woodgett, J, Dedhar, S, Gray, V, Delcommenne, M, Tan, C	Proc Natl Acad Sci U S A	1998
7637810	Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction Coffer, PJ, Burgering, BM	Nature	1995

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)

Zhao, JJ (2012-08-13)

Messina, F (2022-02-18)

Yuzugullu, H (2012-08-13)

Thorpe, L (2012-08-13)

Created