◀ Back to AKT1
AKT1 — FOXO4
Pathways - manually collected, often from reviews:
-
OpenBEL Selventa BEL large corpus:
FOXO4
→
AKT1
(increases, FOXO4 Activity)
Tang et al., J Biol Chem 2002*
Evidence: From full text: In tumor cells AKT phosphorylates transcription factor AFX in PI3-kinase signaling pathway Phosphorylated AFX could not translocate to nucleus for its further activity Mutant AFX was derived to inhibit its phosphorylation
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OpenBEL Selventa BEL large corpus:
FOXO4
→
AKT1
(directlyIncreases, FOXO4 Activity)
Brunet et al., J Cell Biol 2002
Evidence: To investigate the normal intracellular distribution of 14-3-3 proteins and their ligands, U2OS cells were immunostained with a polyclonal antibody that recognizes all 14-3-3 isotypes (pan-14-3-3) or with a monoclonal antibody generated against the 14-3-3sigma isotype (Fig. 1 A). Upon growth factor stimulation, Akt is activated, directly phosphorylating FKHRL1 at T32 and S253, and to a lesser extent at S315, and resulting in FKHRL1 relocalization from the nucleus to the cytoplasm .... Similar A...
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NCI Pathway Database Regulation of nuclear SMAD2/3 signaling:
AKT1 (AKT1)
→
FOXO1-3a-4 (FOXO3/FOXO4/FOXO1)
(modification, activates)
Seoane et al., Cell 2004
Evidence: mutant phenotype
-
NCI Pathway Database Class I PI3K signaling events mediated by Akt:
AKT1 (AKT1)
→
FOXO1-3a-4-inactive (FOXO3/FOXO4/FOXO1)
(modification, activates)
Brunet et al., Cell 1999
Evidence: mutant phenotype, assay
-
NCI Pathway Database Class I PI3K signaling events mediated by Akt:
AKT1 (AKT1)
→
FOXO1-3a-4 (FOXO3/FOXO4/FOXO1)
(modification, activates)
Brunet et al., Cell 1999
Evidence: mutant phenotype, assay
-
Reactome Reaction:
AKT1
→
FOXO4
(reaction)
Brunet et al., Cell 1999, Rena et al., J Biol Chem 1999, Matsuzaki et al., J Biochem 2005*, Carpten et al., Nature 2007*
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WikiPathways PI3K-AKT-mTOR signaling pathway and therapeutic opportunities:
AKT1
→
FOXO3/FOXO1/BAD/CDKN1B/GSK3B/FOXO4
(activation)
-
WikiPathways Signaling Pathways in Glioblastoma:
AKT1/AKT2/AKT3
→
FOXO1/FOXO3/FOXO4
(mim-inhibition)
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
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IRef Bind_translation Interaction:
AKT1
—
FOXO4
(affinity chromatography technology)
Yang et al., Oncogene 2005*
-
IRef Bind_translation Interaction:
AKT1
—
FOXO4
(coimmunoprecipitation)
Yang et al., Oncogene 2005*
-
IRef Hprd Interaction:
AKT1
—
FOXO4
(in vitro)
Kops et al., Nature 1999, Brownawell et al., Mol Cell Biol 2001, De Ruiter et al., Mol Cell Biol 2001*, Matsuzaki et al., J Biochem 2005*
-
IRef Hprd Interaction:
AKT1
—
FOXO4
(in vivo)
Kops et al., Nature 1999, Brownawell et al., Mol Cell Biol 2001, De Ruiter et al., Mol Cell Biol 2001*, Matsuzaki et al., J Biochem 2005*
-
IRef Innatedb Interaction:
AKT1
—
FOXO4
(unknown, -)
Obsil et al., Biochemistry 2003*
-
IRef Ophid Interaction:
AKT1
—
FOXO4
(aggregation, confirmational text mining)
Brownawell et al., Mol Cell Biol 2001
-
IRef Ophid Interaction:
AKT1
—
FOXO4
(aggregation, interologs mapping)
Brown et al., Bioinformatics 2005
Text-mined interactions from Literome
Tsai et al., Endocrinology 2003
(Carcinoma, Hepatocellular...) :
The activity of
FOXO proteins is principally
regulated by activation of protein kinase B
(PKB)/Akt by insulin and other cytokines
Sandri et al., Cell 2004
(Muscular Atrophy) :
IGF-1 treatment or
AKT overexpression
inhibits Foxo and atrogin-1 expression
Bouchard et al., EMBO J 2004
(Cell Transformation, Neoplastic) :
Myc induced proliferation and transformation require
Akt mediated phosphorylation of
FoxO proteins
Kuiperij et al., Oncogene 2005
:
We show that in MEFs cAMP strongly
induces transcriptional activation of
FoxO4 through the inhibition of
PKB
Yang et al., Oncogene 2005
(Cell Transformation, Neoplastic) :
Constitutively active
FOXO4 inhibits
Akt activity,
regulates p27 Kip1 stability, and suppresses HER2 mediated tumorigenicity ... We found that
FOXO4A3 inhibited the kinase activity of
protein kinase B/Akt and reversed HER2 mediated p27 mislocation in the cytoplasm ... We found that
FOXO4A3 inhibited the kinase activity of protein kinase
B/Akt and reversed HER2 mediated p27 mislocation in the cytoplasm
Vogt et al., Cell cycle (Georgetown, Tex.) 2005
:
Activation of
Akt by growth factors
results in phosphorylation of nuclear
FOXO at specific sites followed by additional phosphorylations mediated by other kinases
Dionne et al., Curr Biol 2006
(Weight Loss) :
FOXO activity is
inhibited by the insulin effector kinase
Akt ; we show that Akt activation is systemically reduced as a result of M. marinum infection
Lavery et al., J Neurosci 2007
:
Our results raise the possibility that neurofibroma formation in individuals with neurofibromatosis might result in part from a
Ras-PI3K-Akt dependent inhibition of
FOXO within Schwann cells
Ni et al., Proc Natl Acad Sci U S A 2007
(Insulin Resistance) :
FoxO activated
Akt directly interacts with and phosphorylates FoxO, providing feedback inhibition ... In addition,
FoxO activity suppresses protein phosphatase 2A (PP2A) and
disrupts Akt-PP2A and Akt-calcineurin interactions ... Repression of Akt-PP2A/B interactions and phosphatase activities contributes, at least in part, to
FoxO dependent increases in
Akt phosphorylation and kinase activity ... Importantly,
FoxO mediated
increases in
Akt activity diminish insulin signaling, as manifested by reduced Akt phosphorylation, reduced membrane translocation of Glut4, and decreased insulin triggered glucose uptake
Evans-Anderson et al., Circ Res 2008
:
Likewise, adenoviral mediated expression of
AKT promotes cardiomyocyte proliferation and cytoplasmic localization of
FOXO
Shankar et al., Journal of molecular signaling 2008
:
Inhibition of
AKT and MEK kinases synergistically
induced FOXO transcriptional activity, which was further enhanced in the presence of EGCG
Park et al., Cell Signal 2009
:
In this study, we found that TRAIL inhibited
PI3K/Akt dependent
FoxO phosphorylation and relocated FoxO proteins into the nucleus from the cytosol in activated human hepatic stellate LX-2 cells
Gross et al., Curr Diab Rep 2009
:
Given the impact of insulin signaling on
Akt mediated phosphorylation of
FOXO and the relatively high expression of Foxo1 in insulin-responsive tissues, this transcription factor is highly poised to regulate energy metabolism
Fritz et al., Oncogene 2010
(Breast Neoplasms) :
CNK1 controls
Akt dependent phosphorylation and transcriptional activity of
FoxO , which is a negative regulator of proliferation
Alam et al., Cell Metab 2010
:
Thus, EAK-7 and
AKT-1 inhibit
DAF-16/FoxO activity via distinct mechanisms
Senf et al., Am J Physiol Cell Physiol 2011
:
Although the
regulation of
FOXO by
Akt is well evidenced in skeletal muscle, the current study demonstrates that FOXO is also regulated in muscle via the histone acetyltransferase ( HAT ) activities of p300/CREB binding protein (CBP)
Senapedis et al., Mol Biol Cell 2011
:
Insulin/Akt activation
directs phosphorylation and cytoplasmic sequestration of
FOXO away from its target genes and serves as an endpoint of a complex signaling network
Mahajan et al., Thromb Haemost 2012
:
In conclusion, thrombin and FoxO factors functionally interact through
PI3K/Akt dependent
FoxO phosphorylation leading to expression of cell cycle regulating genes and ultimately SMC proliferation
Jacquin et al., Cell Death Differ 2013
:
Active
Akt prevents
FoxO nuclear localization, which precludes Bcl-6 expression and leads to Bcl-xL overexpression