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

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

Stable Identifier

R-HSA-9614414

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

nucleoplasm, cytosol

ReviewStatus

5/5

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

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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 Brunet, A, Bonni, A, Zigmond, MJ, Lin, MZ, Juo, P, Hu, LS, Anderson, MJ, Arden, KC, Blenis, J, Greenberg, ME	Cell	1999
10358075	Phosphorylation of the transcription factor forkhead family member FKHR by protein kinase B Rena, G, Guo, S, Cichy, SC, Unterman, TG, Cohen, P	J Biol Chem	1999
16114898	14-3-3 Protein interacts with nuclear localization sequence of forkhead transcription factor FoxO4 Obsilova, V, Vecer, J, Herman, P, Pabianova, A, Sulc, M, Teisinger, J, Boura, E, Obsil, T	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 Matsuzaki, H, Ichino, A, Hayashi, T, Yamamoto, T, Kikkawa, U	J Biochem (Tokyo)	2005