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AKT2 — FOXO1
Pathways - manually collected, often from reviews:
Text-mined interactions from Literome
Tang et al., J Biol Chem 1999
:
Negative
regulation of the forkhead transcription factor
FKHR by
Akt ... We have examined the possible
role of
Akt in the regulation of
FKHR ... These results suggest that
FKHR may be a direct nuclear regulatory
target for
Akt in both metabolic and cell survival pathways
del Peso et al., Oncogene 1999
:
Regulation of the forkhead transcription factor
FKHR , but not the PAX3-FKHR fusion protein, by the serine/threonine kinase
Akt ... Here we show that
Akt , but not inactive Akt,
represses the transcriptional activity of
FKHR , another member of the forkhead family ...
FKHR mutants with alanine substitutions at three Akt phosphorylation consensus sites ( T24, S256 and S319 ) were
inhibited by
Akt , but mutation of all three sites rendered FKHR resistant to suppression ... By contrast, the transcriptional activity of the oncogenic
PAX3-FKHR fusion protein, containing two consensus phosphorylation sites, was not
inhibited by
Akt ... Importantly,
Akt inhibited the translocation of
FKHR to the nucleus, providing a mechanism by which Akt might regulate the transcriptional activity of FKHR ... These results provide evidence that
Akt inhibits the transcriptional activity of
FKHR by controlling its trafficking into the nucleus and that oncogenic PAX3-FKHR can escape this negative regulation by Akt
Tomizawa et al., J Biol Chem 2000
:
Neither site is required for insulin inhibition of promoter activity stimulated by the FKHR fragment, and overexpression of
Akt does not
inhibit FKHR fragment stimulated Gal4 promoter activity
Barthel et al., Biochem Biophys Res Commun 2001
(Carcinoma, Hepatocellular...) :
FKHR was phosphorylated in a PI 3-kinase- and
Akt dependent manner, and was translocated from the nucleus to the cytoplasm in response to insulin
Nakae et al., Biochemistry 2001
:
Conversely, expression of a constitutively active
Akt ( Akt-Myr ) in insulin receptor-deficient hepatocytes
led to an overall increase in the level of
Foxo1 phosphorylation, but failed to induce T ( 24 ) and S ( 316 ) phosphorylation
Perrot et al., J Biol Chem 2003
:
PKB/Akt mediated phosphorylation of
Foxo1 has been shown to result in the inhibition of target gene transcription and to trigger the export of Foxo1 from the nucleus, which is generally believed to explain the subsequent decrease of transcription
Andreucci et al., Kidney Int 2003
(Anoxia...) :
We conclude that PI 3-kinase and Akt are activated after renal ischemia/reperfusion and that
Akt phosphorylation
leads to phosphorylation of
FKHR and FKHRL1, which may affect epithelial cell fate in acute renal failure
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
Shinoda et al., J Clin Invest 2004
(Epilepsy) :
Inhibition of
Akt increased the
FKHR/Bim response and DNA fragmentation within the normally resistant cortex
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
Stayrook et al., Endocrinology 2005
(Carcinoma, Hepatocellular) :
Activation of FXR initiated a cascade involving induction of peroxisome proliferator activated receptor alpha and TRB3 expression that is consistent with stimulation of PEPCK gene expression via interference with a pathway that may involve
Akt dependent phosphorylation of Forkhead/winged helix transcription factor (
FOXO1 )
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
Southgate et al., FASEB J 2005
(Insulin Resistance) :
To determine whether the regulation of
FoxO1 was
Akt dependent , we next treated Akt2 -/- and wild-type mice with or without insulin
Patterson et al., Arterioscler Thromb Vasc Biol 2006
(Insulin Resistance...) :
However, rapamycin potently activates AKT dependent signaling, an effect that overrides the downregulation of this pathway by insulin resistance and that causes phosphorylation of the
AKT dependent transcription factor
FOXO1
Cho et al., Cell Metab 2006
(Diabetes Mellitus, Type 2...) :
Insulin signaling inhibits liver glucose production by inducing nuclear exclusion of the gluconeogenic transcription factor
FOXO1 in an
Akt dependent manner
Matsumoto et al., J Clin Invest 2006
(Insulin Resistance...) :
We show that
FoxO1 regulation of
Akt phosphorylation does not require DNA binding and is associated with repression of the pseudokinase tribble 3 (Trb3), a modulator of Akt activity
Daly et al., Proc Natl Acad Sci U S A 2006
:
In addition, we show that Ang-2, like Ang-1, activates
Tie2/Akt signaling in vivo, thereby
inhibiting the expression of
FOXO1 target genes
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
Liu et al., J Endocrinol 2007
:
Interestingly, overexpression of constitutively active
FOXO1 also
led to activation of MEK and
Akt phosphorylation
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
Lengyel et al., Steroids 2007
:
In response to E2, phosphorylation of
Akt/PKB on Ser473 and FOXO1 on Ser256 and Thr24 residues increased but with distinct kinetics,
regulating the activation and inactivation of Akt and
FOXO1 proteins, respectively
Kim et al., Biogerontology 2008
:
The activation of NF-kappaB through
Akt induced
FOXO1 phosphorylation during aging and its modulation by calorie restriction
Ni et al., Proc Natl Acad Sci U S A 2007
(Insulin Resistance) :
Here, we report that sustained activation of either
FoxO1 or FoxO3 in cardiac myocytes
increases basal levels of
Akt phosphorylation and kinase activity ...
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
Ward et al., Endocrinology 2008
(Endometrial Neoplasms) :
Inhibition of
Akt in Ishikawa cells also
increased nuclear
FOXO1 protein levels
Evans-Anderson et al., Circ Res 2008
:
Likewise, adenoviral mediated expression of
AKT promotes cardiomyocyte proliferation and cytoplasmic localization of
FOXO
Tremblay et al., Cell Metab 2008
(Cardiomegaly...) :
A new study by Ni et al. ( 2007 ) shows that sustained activation of
FoxO1 or FoxO3 in cardiomyocytes selectively
enhances the activity of
Akt/PKB and reduces insulin signaling through inhibition of calcineurin and PP2A
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
Abid et al., Arterioscler Thromb Vasc Biol 2008
:
Incubation of human coronary artery endothelial cells with HGF induced prolonged
PI3K/Akt dependent phosphorylation and nuclear exclusion of
FKHR/FOXO1
Alam et al., Endocrinology 2009
:
These results indicate that FSH stimulated HIF-1 activation leading to up-regulation of targets such as vascular endothelial growth factor requires not only
PI3-kinase/AKT mediated activation of mammalian target of rapamycin as well as phosphorylation of
FOXO1 and possibly MDM2 but also a protein ( kinase ) activity that is inhibited by the classic ERK kinase inhibitor PD98059 but not ERK1/2 or 5
Yamagata et al., Mol Cell 2008
:
PRMT1 methylated FOXO1 at conserved Arg248 and Arg250 within a consensus motif for Akt phosphorylation ; this methylation directly blocked
Akt mediated phosphorylation of
FOXO1 at Ser253 in vitro and in vivo
Shu et al., Hum Mol Genet 2009
:
Loss of TCF7L2 resulted in decreased GLP-1 and GIP stimulated AKT phosphorylation, and
AKT mediated
Foxo-1 phosphorylation and nuclear exclusion
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 ... 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
Wang et al., Peptides 2010
:
Unlike the JNK inhibitor SP600125,
Akt inhibitor IV blocked the anti-lipotoxic effect of ghrelin and
stimulated Foxo1 nuclear translocation
Yoshimochi et al., J Recept Signal Transduct Res 2010
:
Akt induced phosphorylation of
FOXO1 is required for its binding to PCAF, whereas the binding between FOXO1 and CBP is independent on FOXO1 S253 phosphorylation
Fritz et al., Oncogene 2010
(Breast Neoplasms) :
CNK1 controls
Akt dependent phosphorylation and transcriptional activity of
FoxO , which is a negative regulator of proliferation
Bar et al., PloS one 2010
:
Time resolved live imaging of
AKT dependent
FoxO1 phosphorylation revealed that miR-22 accelerated AKT activity upon growth factor stimulation, and attenuated its down regulation by serum withdrawal
Wu et al., Cancer Res 2010
(Breast Neoplasms) :
Blocking the constitutively active
Akt by a specific Akt/protein kinase B signaling inhibitor-2 ( API-2 ) significantly
increased FOXO1A expression and rendered the cells more responsive to trastuzumab induced growth inhibition
Kyo et al., Clin Cancer Res 2011
:
Disrupting
Akt activity by the introduction of the dominant negative form of Akt
increased nuclear
FOXO1 accumulation and enhanced the effect of progestin
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
Tsuchiya et al., Arterioscler Thromb Vasc Biol 2011
(Inflammation) :
Deacetylated
FoxO1 inhibits free cholesterol induced
Akt phosphorylation and increases levels of the nuclear factor-?B precursor p105, decreasing nuclear translocation of nuclear factor-?B p65 subunit and dampening mitogen activated protein/extracellular signal regulated kinase activation to prevent inflammation
Frampton et al., Gut 2012
(Bile Duct Neoplasms...) :
The effect of progranulin on proliferation and
Akt activation and subsequent effects of
FOXO1 phosphorylation were assessed in vitro
Yin et al., J Clin Endocrinol Metab 2012
(Endometriosis...) :
Moreover, inhibition of
AKT with MK2206, an allosteric AKT inhibitor, dramatically
increased the accumulation of nuclear
FOXO1 as well as expression of IGFBP1
Lai et al., J Agric Food Chem 2012
:
In addition, Xanthigen may also stimulate insulin trigger signaling and result in
Akt dependent phosphorylation of
forkhead/winged helix O (FoxO)1 and FoxO3a
Jothi et al., Cell cycle (Georgetown, Tex.) 2012
(Disease Models, Animal...) :
We observed that low levels of AKT activity are associated with elevated levels of PAX3-FKHR transcriptional activity, and
AKT hyperactivation
results in
PAX3-FKHR phosphorylation coupled with decreased activity once cells are under differentiation-permissible conditions ... Thus,
AKT regulation of the PAX3-
FKHR suppresses myogenic gene expression in ARMS cells, causing a failure in differentiation
Tabassam et al., Helicobacter 2012
(Helicobacter Infections) :
Inhibition of PI3K or
Akt kinase activity
reduced FoxO1/3a phosphorylation ... Infection with oipA mutants reduced PI3K/Akt activation and inhibited FoxO1/3a phosphorylation, whereas infection with cag PAI mutants reduced
PI3K/Akt activity but did not
inhibit FoxO1/3a activation
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