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FOXO3 — IGF1
Text-mined interactions from Literome
Zheng et al., J Biol Chem 2000
:
Insulin-like growth factor-1 induced phosphorylation of the forkhead family transcription factor
FKHRL1 is mediated by Akt kinase in PC12 cells ... In this study, we characterized the phosphorylation of
FKHRL1 induced by
IGF-1 in PC12 cells and various neuronal cell types and examined the potential role of Akt in this regard ...
IGF-1 rapidly
induced the phosphorylation of Akt and
FKHRL1 in PC12 cells ... The phosphorylation of Akt and FKHRL1 induced by 10 nm IGF-1 was inhibited by the phosphatidylinositide 3-kinase (PI3K) inhibitors wortmannin ( 0.25-2 microm ) and LY294002 ( 12.5-100 microm ), but not by the MEK inhibitor PD98059 ( 50 microm ) or the p70 S6 kinase pathway inhibitor rapamycin ( 50 nm ), suggesting that the phosphorylation of
FKHRL1 induced by
IGF-1 is mediated by the PI3K pathway ... Moreover, transient expression of constitutively active Akt ( MS-Akt, where MS is a myristylation signal ) increased the phosphorylation of FKHRL1, whereas the expression of kinase-dead Akt ( M179A Akt ) attenuated the phosphorylation of
FKHRL1 induced by 10 nm
IGF-1 in PC12 cells ... As
IGF-1 also
induced the phosphorylation of
FKHRL1 in primary cortical and cerebellar neuronal cultures, these data, taken together, demonstrate that IGF-1, acting via the PI3K/Akt kinase pathway, can regulate the phosphorylation of FKHRL1, leading to inhibition of this apoptotic transcription factor in neuronal cells
Zheng et al., Mol Pharmacol 2002
:
Insulin-like growth factor-1 induced phosphorylation of transcription factor
FKHRL1 is mediated by phosphatidylinositol 3-kinase/Akt kinase and role of this pathway in insulin-like growth factor-1 induced survival of cultured hippocampal neurons ... We report herein that
IGF-1 rapidly
induced the phosphorylation of endogenous
FKHRL1 in hippocampal neurons ...
IGF-1 blocked the nuclear translocation of
FKHRL1 in hippocampal neurons and promoted survival in parallel to the phosphorylation of Akt and FKHRL1
Pene et al., Oncogene 2002
(Multiple Myeloma) :
IGF-1 but not IL-6
increased phosphorylation of Akt,
FKHRL-1 and P70 ( S6K )
Green et al., J Biol Chem 2004
(Breast Neoplasms...) :
In addition we show that the loss of IRS-1 after MKK1 inhibition prevents
IGF mediated phosphorylation of
FKHRL1
Skurk et al., J Biol Chem 2005
(Cardiomegaly) :
FOXO3a gene transfer
prevented both
IGF and stretch induced hypertrophy in rat neonatal cardiac myocyte cultures in vitro
Schwab et al., Apoptosis 2005
(Neuroblastoma) :
IGF-I induced phosphorylation of Erks ( p42/p44 ), FKHR ( FOXO1a ) ( Ser 253 ),
FKHRL1 ( FOXO3a ) ( Ser 256 ), and Akt ( Ser 473 ) ... PI3-K inhibitor, LY294002, reduced
IGF-I stimulated phosphorylation of FKHR,
FKHRL1 , and Akt, but did not affect Erk phosphorylation ... Leptomycin B, an inhibitor of Crm1 mediated nuclear export, decreased the level of
FKHRL1 phosphorylation in the
presence of
IGF-I in vector and FKHR overexpressing cells, but had no effect on the phosphorylation status of FKHR
Hansen et al., PLoS Genet 2008
:
Long lived daf-2
insulin/IGF-1 receptor mutants
require both autophagy and the transcription factor
DAF-16/FOXO for their longevity, but we find that autophagy takes place in the absence of DAF-16
Hilmi et al., Pigment Cell Melanoma Res 2008
(Melanoma) :
In melanoma cells, we show that
IGF1 , which exerts pro-survival properties,
induces the phosphorylation and nuclear exclusion of
FKHRL1 in a PI3K/AKT dependent pathway
Li et al., Rejuvenation Res 2008
(Calcium Signaling...) :
Aging and
IGF-1 deficiency significantly
reduced expression of the transcriptional factor
Foxo3a without an overt effect on the mammalian target of rapamycin (mTOR) level
Essaghir et al., J Biol Chem 2009
:
PDGF, fibroblast growth factors ( FGF ), and
IGF-I repressed the expression of
FOXO genes in human fibroblasts
Seiliez et al., Comp Biochem Physiol B Biochem Mol Biol 2010
:
Our in vitro study on trout myocytes indicated that
IGF1 induces
FoxO3 phosphorylation but has a low or no effect on autophagy related gene expression, suggesting a moderate role for this transcription factor on the autophagic/lysosomal pathway in this species
Kenyon et al., Ann N Y Acad Sci 2010
:
However, the mechanisms by which inhibition of
insulin/IGF-1 signaling and germline loss
activate DAF-16/FOXO are distinct
Löw et al., Gen Comp Endocrinol 2011
(Nerve Degeneration) :
Longevity increases when
FoxO becomes activated in
response to reduced
insulin/IGF-1 signalling
Sengupta et al., Circ Res 2013
:
In vivo, combined loss of FoxO1 and
FoxO3 specifically in cardiomyocytes
leads to delayed cell-cycle withdrawal and increased expression of
IGF1 and FoxM1
Osuka et al., Stem Cells 2013
(Glioma) :
In the resting state, continuous
IGF1 stimulation ultimately
induces downregulation of Akt/extracellular-signal regulated kinases ( ERK ) and
FoxO3a activation, which results in slower proliferation and enhanced self-renewal