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AKT1 — IGF2
Text-mined interactions from Literome
Ahmad et al., J Immunol 2000
:
In F/V cells,
IGF-1 increased
PKB , PDE3B, and PDE4 activities approximately 2-fold ... In F/B cells,
IGF-1 , in a wortmannin-sensitive manner,
increased PKB activity approximately 10-fold and PDE3B phosphorylation and activity ( approximately 4-fold ), but increased PDE4 to the same extent as in F/V cells ... In F/B* cells,
IGF-1 had little further effect on
PKB and activation/phosphorylation of PDE3B
Tu et al., Cancer Res 2000
(MAP Kinase Signaling System...) :
In correlation with activation of PI 3-K,
IGF-I also effectively activated the AKT kinase in 8226 and OCI-My5 cells, and IL-6
activated AKT in AF-10 and MH.60 cells
Trümper et al., Ann N Y Acad Sci 2000
:
Insulin,
IGF-1 , and GLP-1
induced distinctive time dependent, dose dependent, and glucose dependent phosphorylation of
PKB/Akt ... Insulin,
IGF-1 , and GLP-1
induced distinctive time dependent, dose dependent, and glucose dependent phosphorylation of
PKB/Akt
Tanno et al., Cancer Res 2001
(Neoplasm Invasiveness...) :
We demonstrate here that
AKT regulates
IGF-IR expression in PANC-1 and AsPC-1 cells ... Overexpression of wild-type or constitutively active
AKT ( i.e., AKT1 or AKT2 ) also
resulted in elevated
IGF-IR expression ... Furthermore,
AKT induced
IGF-IR expression was down-regulated by dominant negative Src or PTEN ... These data provide evidence for a link between
AKT signaling and the
regulation of
IGF-IR expression and demonstrate that active AKT promotes the invasiveness of pancreatic cancer cells through the up-regulation of IGF-IR expression
Sumitomo et al., Cancer Res 2001
(Prostatic Neoplasms) :
Incubation of TSU-Pr1 cells with specific kinase inhibitors together with ET-1 or bombesin showed that
IGF-IR activation is
required for neuropeptide induced
Akt phosphorylation, and that neuropeptide induced Akt activation is predominantly mediated by Src and phosphatidylinositol 3-kinase but not by mitogen activated protein kinase or protein kinase C
Wu et al., Oncogene 2001
(Glioblastoma) :
Targeted deletion of the N-terminal SH2 domain of SHP-2 severely impaired PDGF- and
IGF induced
Akt phosphorylation
Klotz et al., J Biol Chem 2002
:
In addition,
IGF-1 stimulated phosphorylation of uterine
Akt and MAPK in both WT and alpha ERKO mice
Varma et al., Cancer Res 2002
(Breast Neoplasms) :
Consistent with this suggestion,
IGF-I induced phosphorylation of extracellular signal regulated kinase,
AKT , and insulin receptor substrate 1 was unaffected by ICI treatment
Adachi et al., Gastroenterology 2002
(Colonic Neoplasms) :
It effectively blocked both IGF-I- and
IGF-II induced activation of
Akt-1
Lee et al., Cancer Gene Ther 2003
(Adenocarcinoma, Bronchiolo-Alveolar...) :
Both
ad-IGF-IR/950 and ad-IGF-IR/482 effectively
blocked IGF-I induced
Akt kinase activation
Duplomb et al., Endocrinology 2003
:
Confirming this idea, ERK1/2 and
AKT/protein kinase B, the kinases necessary for cell proliferation and survival, were
activated by
IGF-II alone or by the association of IL-6-type cytokines and IGF-II ...
Activation of ERK1/2 and
AKT by
IGF-II thus appears essential to sustain cellular expansion driven by IL-6-type cytokines
Moorehead et al., J Biol Chem 2003
:
Transgenic
IGF-II expression also
increased mammary PTEN protein, leading to reductions in
Akt phosphorylation, epithelial proliferation, and mammary morphogenesis
Min et al., Cancer Res 2003
(Pancreatic Neoplasms) :
It effectively blocked both IGF-I and
IGF-II induced activation of
Akt-1
Lu et al., Biochem Biophys Res Commun 2004
(Breast Neoplasms...) :
However,
IGF-I induced tyrosine-phosphorylation of IGF-I receptor and IRS-I and
AKT phosphorylation were unaffected by ErbB2 overexpression
Sivaprasad et al., Endocrinology 2004
(MAP Kinase Signaling System) :
In contrast,
IGF-I induced
Akt activation was maximal between 15 and 90 min and was sustained for 6 h
Tiffin et al., Endocrinology 2004
(MAP Kinase Signaling System) :
Akt phosphorylation is not
sufficient for
insulin-like growth factor stimulated myogenin expression but must be accompanied by down-regulation of mitogen activated protein kinase/extracellular signal regulated kinase phosphorylation
Phornphutkul et al., J Endocrinol 2004
:
In contrast,
IGF-I mediated
Akt activation was unchanged by differentiation, indicating intact upstream IGF-I receptor signaling
Cui et al., J Biol Chem 2005
:
In addition,
IGF-I activated
Akt while inhibiting caspase-3 activation, and these effects were reversed by the PI3K inhibitors LY 294002 and wortmannin, but not by the MEK1 inhibitor PD 98059
Yi et al., J Neurosci 2005
(Diabetic Retinopathy...) :
However,
IGF1 stimulated
Akt phosphorylation was barely detected, and cleaved/activated caspase-3 was significantly elevated in isolated retinas of Irs2-/- mice
Yi et al., Biochem Biophys Res Commun 2005
(Adenocarcinoma...) :
These findings suggest that PTEN may inhibit antiapoptotic IGF actions not only by blocking the
IGF-IGFR induced
Akt activity, but also by regulating expression of components of the IGF system, in particular, upregulation of IGFBP-3, which is known to exert antiproliferative effects through IGF dependent and IGF independent mechanisms in cancer cells
Min et al., Gut 2005
(Neoplasm Invasiveness...) :
IGF-Ir/dn blocked
Akt-1 activation induced by IGF-I, IGF-II, and des ( 1-3 ) IGF-I, but not by insulin
Brywe et al., Eur J Neurosci 2005
(Hypoxia-Ischemia, Brain) :
In conclusion,
IGF-I induces activation of
Akt during recovery after HI which, in combination with inactivation of GSK3beta, may explain the attenuated activation of caspases and reduction of injury in the immature brain
Remacle-Bonnet et al., Am J Pathol 2005
(Carcinoma...) :
However, disruption of rafts by acute cholesterol depletion shifted
IGF-IR to non-raft domains, abolished the IGF-I mediated proapoptotic effect, and
inhibited the IGF-I dependent IRS-1 and
Akt recruitment into and phosphorylation/activation within lipid rafts
Wang et al., Clin Cancer Res 2006
(Carcinoma...) :
Blocking
IGF-IR blocked
Akt phosphorylation and decreased proliferation and microvessel density but increased apoptosis within the tumor xenografts
Wilson et al., J Biol Chem 2006
:
We previously identified an autocrine pathway involving production of
IGF-II and
activation of the IGF-I receptor, phosphatidylinositol 3-kinase, and
Akt in myoblast differentiation induced by MyoD in 10T1/2 mesenchymal stem cells and found that blocking this pathway prevented differentiation ( Wilson, E. M., Hsieh, M. M., and Rotwein, P. ( 2003 ) J. Biol. Chem. 278, 41109-41113 )
Wu et al., Development 2006
:
Kermit 2/XGIPC functions downstream of IGF in eye formation and is required for maintaining
IGF induced
AKT activation
Desbois-Mouthon et al., Int J Cancer 2006
(Carcinoma, Hepatocellular...) :
However, while gefitinib blocked Akt activation by EGF, it had no effect on
Akt activation by
IGF2 and did not cause apoptosis by its own
Azar et al., Can J Physiol Pharmacol 2006
:
Activation of
insulin-like growth factor type-1 receptor is
required for H2O2 induced
PKB phosphorylation in vascular smooth muscle cells
Tanno et al., Clin Cancer Res 2006
(Adrenal Gland Neoplasms...) :
As expected, NVP-AEW541 inhibited
IGF-II mediated stimulation of IGF-IR and
Akt
Tanaka et al., Cancer Res 2006
(Anoxia...) :
Treating the HCC cells with IGF-II or epidermal growth factor (EGF) up-regulated both phospho-Akt and HIF-1alpha, whereas inhibition of IGF-II or EGF signaling down-regulated them both, suggesting that
IGF-II and EGF can, at least in part,
mediate the activation of
Akt and HIF-1alpha ... However,
Akt was not
activated by
IGF-II or EGF in the HIF-1alpha knockdown cells, indicating that expression of the HIF-1 target genes is necessary for the Akt activation
Ogura et al., J Toxicol Sci 2007
:
After induction of differentiation in the presence of 1 microM simvastatin for 2 days,
IGF-1 induced activation of ERK1/2 and
Akt was significantly decreased
Alexia et al., Ann N Y Acad Sci 2006
(Carcinoma, Hepatocellular) :
Drug induced apoptosis was reversed by
IGF-I and this effect was ( i ) dependent on
Akt-1 and -2 phosphorylation and ( ii ) accompanied by the inhibition of initiator caspase-9 activity, suggesting that IGF-IR signaling interferes with mitochondria dependent apoptosis
Borowiec et al., J Cell Physiol 2007
(Breast Neoplasms...) :
In MCF-7 cells,
IGF-1 rapidly
stimulated Akt phosphorylation, whereas IGF-1 had little stimulating effect on Erk 1/2 which seems to be constitutively activated
Levitt et al., Cancer Lett 2007
(Prostatic Neoplasms) :
The hedgehog pathway inhibitor cyclopamine increases levels of p27, and decreases both expression of
IGF-II and
activation of
Akt in PC-3 prostate cancer cells
Knowlden et al., Breast Cancer Res Treat 2008
(Breast Neoplasms...) :
Furthermore, gefitinib significantly enhances
IGF-II mediated phosphorylation of IRS-1 Y612 and
AKT in Tam-R cells
Salani et al., Endocrinology 2008
:
These results demonstrate that : 1 ) Cav-1 down-regulation negatively affects IGF-IR tyrosine phosphorylation ; 2 ) this effect causes a reduced activation of insulin receptor substrate-1, Shc, and
Akt ; and 3 ) Cav-1 is
involved in
IGF-IR antiapoptotic signaling after serum deprivation
Walenkamp et al., J Clin Endocrinol Metab 2008
(Chromosome Deletion...) :
IGF-I binding and type 1
IGF receptor protein expression as well as
activation of type 1 IGF receptor autophosphorylation and protein kinase
B/Akt by IGF-I tended to be lower, but this did not reach statistical significance
Avram et al., Cell Physiol Biochem 2008
:
However,
IGF-1 mediated stimulation of
PKB phosphorylation was not affected by dexa, but ERK phosphorylation was reduced
Carter et al., Acta Neuropathol 2008
(Brain Neoplasms...) :
Aspartyl (asparaginyl)-beta-hydroxylase ( AAH ) is a mediator of neuronal motility, and stimulated by insulin and
IGF activation of PI3
kinase-Akt , or inhibition of GSK-3beta
Codina et al., Gen Comp Endocrinol 2008
:
Metabolic and mitogenic effects of IGF-II in rainbow trout ( Oncorhynchus mykiss ) myocytes in culture and the
role of
IGF-II in the
PI3K/Akt and MAPK signalling pathways
Piao et al., Mol Cancer Ther 2008
(Gastrointestinal Neoplasms) :
NVP-AEW541 blocked autophosphorylation of
IGF-IR and both
Akt and extracellular signal regulated kinase
activation by IGF but not by insulin
Matthews et al., Endocrinology 2008
:
However, in MF ( -/- ) cells,
IGF-I stimulated phosphorylation of
Akt was reduced despite up-regulated Akt levels
Moylan et al., Am J Physiol Cell Physiol 2008
:
TNF increases
AKT phosphorylation ( +50 % ) and stimulation of AKT with
IGF does not
prevent TNF induction of atrogin mRNA
Buck et al., Cancer Res 2008
(MAP Kinase Signaling System...) :
We find for epithelial, but not for mesenchymal-like, tumor cells that
Akt is
controlled cooperatively by EGFR and
IGF-IR
Thomas et al., Prostate 2009
(Prostatic Neoplasms) :
Additionally, inhibition of
IGF-2 activity markedly
attenuated the serum deprivation mediated increase in IGF-IR and
Akt activation, HIF-1alpha expression, and also its own transcription, suggesting autocrine regulation of HIF-1alpha expression via IGF-2 ... Cross-talk between IGF-2/ IGF-IR system and PI3K-Akt pathway was further demonstrated by findings wherein
IGF-IR suppression
inhibited Akt activation, and IGF-IR activation was inhibited following PI3K inhibition
Cao et al., Science signaling 2009
:
Loss of Galpha ( i1 ) and Galpha ( i3 ) severely impaired the activation of
Akt and of p70 S6 kinase and 4E-BP1, downstream targets of mTORC1, in
response to EGF, heparin binding EGF-like growth factor, and transforming growth factor alpha, but not insulin,
insulin-like growth factor , or platelet derived growth factor
Rowzee et al., Endocrinology 2009
:
Although approximately 40 % of IR transcripts were the IGF-II-sensitive IR-A isoform, IGF-II failed to stimulate IR phosphorylation, and an IGF-1R-specific blocking antibody completely abrogated
IGF-II mediated
Akt phosphorylation in the virgin MECs
Yin et al., J Biol Chem 2009
:
In normal human chondrocytes,
IGF-I initiated a strong and sustained phosphorylation of IRS-1 ( Tyr-612 ) and
Akt ( Ser-473 ) and transient ERK phosphorylation
Sunters et al., J Biol Chem 2010
:
Strain related
IGF-IR activation of
AKT requires estrogen receptor alpha (ERalpha) with which IGF-1R physically associates
Wang et al., Invest Ophthalmol Vis Sci 2010
:
Rat lens epithelial explants were used to compare the ability of vitreous,
IGF-1 , PDGF-A, EGF, and FGF-2 to
stimulate the phosphorylation of ERK1/2 and
Akt leading to fiber differentiation, in the presence or absence of selective receptor tyrosine kinase ( RTK ) inhibitors
Jung et al., J Med Food 2010
(Urinary Bladder Neoplasms) :
These results indicate that the inhibition of
IGF-IR signaling and the
activation of
Akt and ERK-1/2 contributed to decreased cell proliferation and increased apoptosis in TSU-Pr1 cells treated with t10c12
Lee et al., Cell Death Differ 2010
:
Furthermore, myogenic activity was highly enhanced with increased
IGF induced
Akt activation in the satellite cells of TRIM72 ( -/- ) mice, compared to those of TRIM72+/+ mice
Ren et al., Proc Natl Acad Sci U S A 2010
(MAP Kinase Signaling System) :
Hypoxia suppresses basal and
IGF induced
Akt-mTOR and p38 activity, whereas it enhances and prolongs IGF induced Erk1/2 activation in a HIF-1 dependent fashion
Zhang et al., Neurochem Res 2011
:
Furthermore,
IGF-1 increased the phosphorylation of
Akt and ERK1/2
Peirce et al., Cancer Chemother Pharmacol 2011
(Neuroblastoma) :
SF1126 blocks MDM2 activation,
IGF-1 induced activation of
Akt , and the upregulation of survivin induced by IGF-1
Xie et al., J Steroid Biochem Mol Biol 2011
(Carcinoma...) :
In parallel,
IGF-II increases phosphorylation of
AKT and p70S6K, while metformin increases AMPK phosphorylation and decreases p70S6K phosphorylation
Li et al., Cancer 2011
(Neovascularization, Pathologic...) :
IGF-IR/dn reduced VEGF expression,
reduced the activation of both
protein kinase B ( Akt ) and mitogen activated protein kinase ( MAPK ), and reduced vascular formation, indicating that IGF-IR/dn inhibited tumor growth in mice by inhibiting both angiogenesis and lymphangiogenesis
Kyathanahalli et al., Biochem Pharmacol 2011
:
Herein, we investigated the putative regulatory roles of protein farnesylation in cell survival signaling pathways in insulin secreting INS 832/13 cells and normal rodent islets, specifically at the level of protein
kinase-B/Akt phosphorylation
induced by insulin-like growth factor
[IGF-1 ]
Madhala-Levy et al., J Cell Physiol 2012
(MAP Kinase Signaling System) :
In cultures derived from Smo ( mut ) ( MCre ; Smo ( flox/flox ) ) mice lacking Smo expression specifically in hindlimb muscles,
IGF-I induced
Akt and p42/44 phosphorylation was significantly reduced compared to IGF-I 's effect on Smo ( cont ) cells
Capp et al., Eur J Obstet Gynecol Reprod Biol 2011
:
Insulin,
IGF I and IGF II
lead to changes in their receptor gene expression and induced
Akt phosphorylation in ESC
Fernandez-L et al., Oncogene 2012
(Cerebellar Neoplasms...) :
Oncogenic YAP promotes radioresistance and genomic instability in medulloblastoma through
IGF2 mediated
Akt activation
Fox et al., Cancer Res 2011
(Adenocarcinoma...) :
Inhibition of InsR and
IGF-IR with the dual tyrosine kinase inhibitor OSI-906 prevented the emergence of hormone independent cells and tumors in vivo,
inhibited parental and LTED cell growth and
PI3K/AKT signaling, and suppressed growth of established MCF-7 xenografts in ovariectomized mice, whereas treatment with the neutralizing IGF-IR monoclonal antibody MAB391 was ineffective
Akundi et al., Neurobiol Dis 2012
:
Moreover,
IGF-1 induced
Akt phosphorylation is impaired in primary cortical neurons from PINK1-deficient mice
Ohashi et al., Cancer Sci 2012
(Biliary Tract Neoplasms) :
BMS-536924 blocked autophosphorylation of
IGF-IR and both
Akt and ERK
activation by both IGF-I and insulin
Zhang et al., J Clin Endocrinol Metab 2012
(Graves Ophthalmopathy) :
Surprisingly,
IGF-I alone did not
increase HAS2 levels, despite significantly increasing the ratio of phosphorylated to total Akt ; furthermore, an
Akt inhibitor increased orbital ( but not sc ) HAS2 transcripts
Bid et al., Mol Cancer Ther 2012
(Neovascularization, Pathologic...) :
SCH717454 blocked IGF-1 stimulated but not
IGF-2 stimulated phosphorylation of
Akt in sarcoma cells
Kent et al., Int J Dev Biol 2012
:
Disruption of
IGF2 did not
affect AKT expression or activation
Appleman et al., Mol Cancer Res 2012
:
Interestingly, we find that activation of
PI3K/AKT signaling occurs downstream of MAP-ERK kinase ( MEK ), and is
dependent on the autocrine activation of the insulin-like growth factor (IGF) receptor ( IGF1R ) by
IGF2
Jiao et al., Mol Cell Biochem 2013
(MAP Kinase Signaling System) :
In addition,
Akt , Erk1/2 MAPK, and p38 MAPK pathways were also
involved in the regulation of basal levels of IGF-I and
IGF-II genes during myogenesis
Willey et al., Int J Radiat Biol 2013
:
Both doses decreased
IGF induced
Akt activation and IGF-1 receptor phosphorylation
Fujita et al., J Biol Chem 2013
:
Inhibitors of IGF1R, Src,
AKT , and ERK1/2 did not
suppress avß3-IGF-IGF1R ternary complex formation, suggesting that activation of these kinases are not required for ternary complex formation
Kessler et al., Am J Physiol Gastrointest Liver Physiol 2013
(Carcinoma, Hepatocellular...) :
Still, p62 transgenic livers do not show liver cell damage but exhibit a pronounced induction of
Igf2 and
activation of the downstream survival kinase
AKT
Bid et al., Clin Cancer Res 2013
(Disease Models, Animal...) :
The IGF ligand binding antibody MEDI-573 suppressed
Akt phosphorylation
induced by exogenous IGF-I and
IGF-2 in sarcoma cells
Arroba et al., Invest Ophthalmol Vis Sci 2013
(Disease Models, Animal...) :
IGF-IR mediated
Akt signaling was evaluated in IGF-I stimulated retinal explants
Dong et al., Am J Physiol Endocrinol Metab 2013
(Fibrosis) :
Using immunoprecipitation assay, we found an interaction between p-Akt or Akt with Smad3 in wild-type mouse muscles and in C2C12 myoblasts ; importantly,
IGF-I increased
p-Akt and Smad3 interaction, whereas TGF-ß1 decreased it ... Therefore, in muscles of IGF-IR ( +/- ) mice, the reduction in
IGF-IR reduces
p-Akt , allowing for dissociation and nuclear translocation of Smad3 to enhance the TGF-ß1 signaling pathway, leading to fibrosis
Ou et al., PloS one 2013
:
We found that
IGF can
activate IGFR and downstream
AKT signaling activities in all the HCC cells tested, but the growth stimulating effect of IGF was most prominent in Hep3B cells ... NVP-AEW541 can abrogate
IGF induced activation of IGFR and
AKT signaling in HCC cells
Huang et al., Stem cell research 2013
(Osteoporosis) :
The mechanism dissection studies revealed that AR deficiency suppressed osteogenesis related genes to inhibit osteoblast differentiation from BMSCs. Knockout of AR promoted adipogenesis of BMSCs via
Akt activation through IGFBP3 mediated
IGF signaling, and the 5 ' promoter assay and chromatin immunoprecipitation assays further proved that AR could modulate IGFBP3 expression at the transcriptional level
Cichy et al., J Biol Chem 1998
:
Protein kinase
B/Akt mediates effects of insulin on hepatic
insulin-like growth factor binding protein-1 gene expression through a conserved insulin response sequence ...
Protein kinase B/Akt mediates effects of insulin on hepatic
insulin-like growth factor binding protein-1 gene expression through a conserved insulin response sequence
Hayashi et al., J Biol Chem 1998
:
In cultured cells,
IGF-I specifically
activated phosphatidylinositol 3-kinase ( PI3-kinase ) and its downstream target,
protein kinase B , but not mitogen activated protein kinases