AKT-phosphorylated FOXO1,FOXO3,FOXO4 translocate to the cytosol

Stable Identifier
Reaction [omitted]
Homo sapiens
Locations in the PathwayBrowser
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

AKT-mediated phosphorylation results in exclusion of FOXO1 (Rena et al. 2001), FOXO3 (Brunet et al. 1999) and FOXO4 (Obslova et al. 2005) from the nucleus. In the absence of PI3K/AKT signaling, FOXO1 (Rena et al. 2001), FOXO3 (Brunet et al. 1999) and FOXO4 (Matsuzaki et al. 2005) are mainly nuclear, but after activation of PI3K/AKT signaling, they become cytoplasmic. One of the conserved AKT phosphorylation sites is within the nuclear localization signal (NLS) of FOXO1, FOXO3 and FOXO4.
In contrast to other FOXO family members, FOXO6 remains predominantly nuclear irrespective of growth factor-induced signaling, and only a small portion of FOXO6 phosphorylated on putative AKT sites may shuttle to the nucleus (Jacobs et al. 2003, van der Heide et al. 2005).

Literature References
PubMed ID Title Journal Year
10102273 Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor

Hu, LS, Bonni, A, Brunet, A, Blenis, J, Zigmond, MJ, Anderson, MJ, Lin, MZ, Greenberg, ME, Juo, P, Arden, KC

Cell 1999
10358075 Phosphorylation of the transcription factor forkhead family member FKHR by protein kinase B

Unterman, TG, Guo, S, Cichy, SC, Rena, G, Cohen, P

J Biol Chem 1999
16114898 14-3-3 Protein interacts with nuclear localization sequence of forkhead transcription factor FoxO4

Sulc, M, Boura, E, Obsil, T, Obsilova, V, Pabianova, A, Vecer, J, Teisinger, J, Herman, P

Biochemistry 2005
16272144 Regulation of intracellular localization and transcriptional activity of FOXO4 by protein kinase B through phosphorylation at the motif sites conserved among the FOXO family

Kikkawa, U, Yamamoto, T, Hayashi, T, Ichino, A, Matsuzaki, H

J Biochem (Tokyo) 2005
Orthologous Events
Cite Us!