◀ Back to AKT3
AKT3 — GSK3B
Pathways - manually collected, often from reviews:
-
OpenBEL Selventa BEL large corpus:
GSK3B
→
AKT3
(directlyIncreases, GSK3B Activity)
Berwick et al., J Biol Chem 2002*
Evidence: PKB also plays an important role in the stimulaiton of glycogen synthase by insulin via the phosphoryaltion and inactivation of glycogen synthase kinase-3
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KEGG Focal adhesion:
AKT1/AKT2/AKT3
→
GSK3B
(protein-protein, inhibition)
-
KEGG T cell receptor signaling pathway:
AKT1/AKT2/AKT3
→
GSK3B
(protein-protein, inhibition)
-
KEGG B cell receptor signaling pathway:
AKT1/AKT2/AKT3
→
GSK3B
(protein-protein, inhibition)
-
KEGG Neurotrophin signaling pathway:
AKT1/AKT2/AKT3
→
GSK3B
(protein-protein, inhibition)
-
KEGG Insulin signaling pathway:
AKT1/AKT2/AKT3
→
GSK3B
(protein-protein, inhibition)
-
KEGG Hepatitis C:
AKT1/AKT2/AKT3
→
GSK3B
(protein-protein, inhibition)
-
KEGG Measles:
AKT1/AKT2/AKT3
→
GSK3B
(protein-protein, inhibition)
-
KEGG Pathways in cancer:
AKT1/AKT2/AKT3
→
GSK3B
(protein-protein, inhibition)
-
KEGG Colorectal cancer:
AKT1/AKT2/AKT3
→
GSK3B
(protein-protein, phosphorylation)
-
KEGG Prostate cancer:
AKT1/AKT2/AKT3
→
GSK3B
(protein-protein, inhibition)
-
KEGG ErbB signaling pathway:
AKT1/AKT2/AKT3
→
GSK3B
(protein-protein, inhibition)
-
KEGG Chemokine signaling pathway:
AKT1/AKT2/AKT3
→
GSK3A/GSK3B
(protein-protein, inhibition)
-
WikiPathways ESC Pluripotency Pathways:
AKT3/AKT2/AKT1
→
GSK3B
(inhibition)
-
WikiPathways ErbB Signaling Pathway:
AKT3
→
GSK3B
(inhibition)
-
WikiPathways Focal Adhesion-PI3K-Akt-mTOR-signaling pathway:
AKT1/AKT3/AKT2
→
GSK3B
(inhibition)
-
WikiPathways Focal Adhesion:
AKT1/AKT2/AKT3
→
GSK3B
(inhibition)
-
WikiPathways Chemokine signaling pathway:
AKT1/AKT2/AKT3
→
GSK3B
(inhibition)
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
Text-mined interactions from Literome
Bijur et al., J Neurochem 2000
:
Because
Akt inhibits
glycogen synthase kinase-3beta ( GSK-3beta ), an enzyme that facilitates cell death, we tested if GSK-3beta is a negative regulator of HSF-1 activation ... Thus, heat shock induced activation of PI-3K and the inhibitory effect of GSK-3beta on HSF-1 activation and HSP-70 expression imply that
Akt induced inhibition of
GSK-3beta contributes to the activation of HSF-1
Chen et al., Cancer Res 2001
(Fibrosarcoma) :
Activation of
Akt by hypoxia
resulted in the phosphorylation of GSK-3alpha and
GSK-3beta at Ser-9 and Ser-21, two well documented Akt phosphorylation sites, respectively, that are inactivating modifications of each GSK-3 isoform
Lenferink et al., Cancer Res 2001
(Breast Neoplasms...) :
The inhibition of
PI3K/Akt resulted in increased activity of
glycogen synthase kinase-3beta , which phosphorylated cyclin D1, potentially reducing its steady-state levels
Ballou et al., J Biol Chem 2001
:
One pathway
inhibits insulin induced
GSK-3beta phosphorylation by blocking insulin activation of
Akt
Grimes et al., J Neurochem 2001
:
Activation of
Akt ( protein kinase B ) with serum increased phospho-serine-9-GSK3 beta ( the inactive form of the enzyme ),
inhibited GSK3 beta activity, and increased CREB DNA binding activity
Satyamoorthy et al., Cancer Res 2001
(Disease Progression...) :
IGF-1 also activated
Akt ,
inhibited its down-stream effector
GSK3-beta , and stabilized beta-catenin
Hardt et al., Circ Res 2002
(Cardiomegaly) :
The activity of
GSK-3beta is negatively
regulated by protein kinase
B/Akt and by the Wnt signaling pathway
Mai et al., J Neurochem 2002
(Neuroblastoma) :
Overexpression of
GSK3beta did not
affect BDNF induced phosphorylation of
Akt , ERK1/2, or FKHRL1, but abolished CREB phosphorylation induced by BDNF
Leis et al., Mol Carcinog 2002
(Cell Transformation, Neoplastic...) :
The data obtained with Akt transformed keratinocytes clearly suggested the
involvement of
Akt in serine 9 phosphorylation of
GSK-3beta
Mottet et al., J Biol Chem 2003
(Anoxia...) :
In conclusion, hypoxia induced a biphasic effect on HIF-1alpha stabilization with accumulation in early hypoxia, which depends on an active PI3K/Akt pathway and an inactive GSK3beta, whereas prolonged hypoxia results in the inactivation of
Akt and
activation of
GSK3beta , which then down-regulates the HIF-1 activity through down-regulation of HIF-1alpha accumulation
Beaulieu et al., Proc Natl Acad Sci U S A 2004
:
In the mouse striatum, increased DA neurotransmission arising either from administration of amphetamine or from the lack of the DA transporter results in inactivation of
Akt and concomitant
activation of GSK-3alpha and
GSK-3beta
Takada et al., J Biol Chem 2004
:
Most surprisingly, TNF induced
Akt activation also
required the presence of
GSK-3beta
Kuemmerle et al., Am J Physiol Gastrointest Liver Physiol 2005
:
In other cell types,
Akt dependent phosphorylation of
glycogen synthase kinase-3 beta ( GSK-3 beta ) inhibits its activity and its ability to stimulate apoptosis ... The aim of the present study was to determine whether endogenous IGF-I regulates
Akt dependent
GSK-3 beta phosphorylation and activity and whether it regulates apoptosis in human intestinal muscle cells
Armstrong et al., Am J Physiol Cell Physiol 2005
(Hypertrophy) :
However, in the heart, a Wnt independent mechanism involving
Akt mediated phosphorylation of
glycogen synthase kinase (GSK)-3beta was recently shown to activate beta-catenin and regulate cardiomyocyte growth
Abbosh et al., Thyroid 2005
(Thyroid Neoplasms) :
Activation of
AKT by phosphatidylinositide-3 kinase (PI3K), a RAS effector,
results in
GSK3beta phosphorylation and deactivation and subsequent beta-catenin upregulation in thyroid cancer
Bhattacharya et al., Apoptosis 2005
:
These data indicate that
Akt regulates the mitochondrial pathway, preventing activation of caspase-9 and thereby caspase-3 via NF-kappaB and these effects are
independent of
GSK-3beta activity
Wong et al., Life Sci 2005
(Enterovirus Infections) :
The activity of
GSK3beta , a downstream target of these pathways, was negatively
regulated by the activation of both MAPK/ERK and
PI3K/Akt
Almeida et al., J Biol Chem 2005
:
Wnt3a induced phosphorylation of
GSK-3beta and downstream activation of beta-catenin mediated transcription
required ERK, PI3K, and
Akt signaling
Tan et al., Cancer Res 2006
:
Protein kinase
B/Akt dependent phosphorylation of
glycogen synthase kinase-3beta in irradiated vascular endothelium ... Overexpression of the dominant negative mutant
Akt attenuated
GSK-3beta phosphorylation at Ser9 and enhanced radiation induced apoptosis ... These data indicate that on exposure of vascular endothelium to ionizing radiation, activation of
Akt signaling
contributes to
GSK-3beta inhibition, which in turn promotes endothelial cell survival and capillary formation
Takai et al., J Cell Biochem 2006
:
The sphingosine 1-phosphate induced phosphorylation of
GSK-3beta was
suppressed by
Akt inhibitor
Shin et al., Cell Signal 2006
(Glioblastoma) :
The inhibition of
Akt resulted in the dephosphorylation of GSK-3beta and
increased GSK-3beta kinase activity
Soriano et al., J Neurosci 2006
(Synaptic Transmission) :
Key mediators of synaptic NMDA receptor dependent neuroprotection, phosphatidylinositol 3
kinase-Akt ( PI3 kinase-Akt ) signaling to Forkhead box subgroup O ( FOXO ) export and
glycogen synthase kinase 3beta ( GSK3beta )
inhibition and cAMP response element binding protein dependent ( CREB dependent ) activation of brain derived neurotrophic factor (BDNF), can be induced only by low doses of NMDA via this action potential dependent route
Ito et al., EMBO Rep 2006
:
Sema4D suppressed R-Ras activity in hippocampal neurons, in parallel with dephosphorylation of
Akt and
activation of
glycogen synthase kinase (GSK)-3beta ... The R-Ras GAP activity was necessary for plexin-B1 induced dephosphorylation of
Akt and
activation of
GSK-3beta and was also required for phosphorylation of a downstream kinase of GSK-3beta, collapsin response mediator protein-2
Hanai et al., J Cell Biochem 2006
:
The PDGF-BB induced
GSK-3beta phosphorylation was
suppressed by the
Akt inhibitor
Lin et al., J Am Soc Nephrol 2006
(Diabetes Mellitus, Experimental...) :
Pharmacologic inhibition of
GSK-3beta by recombinant Wnt5a or bromoindirubin-3'-oxime or LiCl
increased Akt phosphorylation and beta-catenin translocation and abrogated high glucose mediated proapoptotic activities
Ishibe et al., Mol Cell Biol 2006
:
In nonconfluent cells treated with HGF, the high level of
Akt activation
resulted in inhibitory phosphorylation of
glycogen synthase kinase 3beta ( GSK-3beta ) and increased beta-catenin nuclear signaling
Min et al., Exp Cell Res 2007
:
Transient overexpression of a kinase-deficient
Akt mutant remarkably
suppressed GSK-3beta activation and cell death
Vaidya et al., Cell Mol Life Sci 2006
:
Akt mediated
GSK-3beta inhibition prevents migration of polyamine depleted intestinal epithelial cells via Rac1
Corasaniti et al., Br J Pharmacol 2007
:
In addition to preventing ROS accumulation and activation of calpain, BEO ( 0.01 % ) counteracted the deactivation of
Akt and the consequent
activation of
GSK-3beta , induced by NMDA
Hazeki et al., Biol Pharm Bull 2007
:
The resultant activation of a serine-threonine protein kinase
Akt leads to the phosphorylation of
glycogen synthase kinase (GSK)-3beta , which is active in resting cells but is inactivated by phosphorylation
Li et al., J Biol Chem 2007
(Anoxia...) :
Adenoviral expression of constitutively active
AKT and lithium chloride
mediated inhibition of
GSK3beta reduce the potentiated programmed cell death elicited by pleiotrophin
Das et al., FEBS Lett 2007
:
More importantly, we demonstrate that TGFbeta significantly abolished
Akt mediated serine-9 phosphorylation of
glycogen synthase kinase 3beta ( GSK3beta ), thus prevented its inactivation
Rojo et al., J Neurochem 2008
:
Thus, H2O2 rapidly activated
Akt ,
inhibited GSK-3beta , and directed the transcription factor Nrf2 to the nucleus, but after 4 h Akt was inactive, GSK-3beta was active and Nrf2 was more cytosolic than nuclear
Nishimoto et al., J Neurosci Res 2008
(Brain Ischemia...) :
These findings suggest that AMPA activates
PI3K-Akt and subsequently
inhibits GSK3beta and that inactivated GSK3beta attenuates glutamate induced caspase-3 cleavage and neurotoxicity
Li et al., Mol Cancer Ther 2007
(Neuroblastoma) :
BDNF activation of TrkB induced the
Akt dependent phosphorylation of
GSK-3beta , resulting in its inactivation
Duarte et al., Biochim Biophys Acta 2008
:
Since phosphatidylinositol 3-kinase
(PI-3K)/Akt mediated inhibition of
GSK-3beta may stimulate protein synthesis and decrease apoptosis, we analysed mRNA and protein expression of `` candidate '' proteins involved in antioxidant defense, glucose metabolism and apoptosis
Thornton et al., Science 2008
:
Although the protein kinase
Akt inhibits
GSK3beta by phosphorylation at the N terminus, preventing Akt mediated phosphorylation does not affect the cell-survival pathway activated through the GSK3beta substrate beta-catenin
LaMarca et al., Hum Reprod 2008
:
Although
Akt activation
leads to
GSK-3beta phosphorylation and the subsequent expression of beta-catenin, activation of this pathway by 1-azakenpaullone was insufficient to stimulate the motile phenotype
Mariappan et al., J Biol Chem 2008
(Diabetes Mellitus, Type 2...) :
Dominant negative
Akt , but not dominant negative p70S6 kinase,
inhibited GSK3beta phosphorylation induced by high glucose and high insulin, suggesting Akt but not p70S6 kinase was upstream of GSK3beta
Shukla et al., Mol Carcinog 2009
(Prostatic Neoplasms) :
Inhibition of
p-Akt by apigenin
resulted in decreased phosphorylation of
GSK-3beta along with decreased expression of cyclin D1 and increased expression of p27/kip1
Dal Col et al., Cell cycle (Georgetown, Tex.) 2008
(Lymphoma, Mantle-Cell) :
Here we show that inhibition of
PI3-K/Akt induces a 40 % decrease of cyclin D1 half-life as a
result of accumulation of the dephosphorylated/active form of
GSK-3beta within the nucleus, where this kinase can phosphorylate cyclin D1 on Thr286 thereby promoting its nuclear export
Russo et al., J Neurochem 2008
(Ischemia...) :
Using an experimental model of retinal ischemia induced by transiently raise the intraocular pressure ( IOP ), In this study, we report the original observation that ischemic retinal ganglion cells death is associated with the transient deactivation of the pro-survival kinase
Akt and
activation of
GSK-3beta followed, during reperfusion, by a longer lasting, PI3K dependent, activation of Akt and phosphorylation of GSK-3beta
Neznanova et al., Int J Neuropsychopharmacol 2009
:
Here, we report that acute ethanol challenge, at a dose commonly regarded as reinforcing, strongly phosphorylates glycogen synthase kinase-3beta ( GSK-3beta ) in this region with corresponding increased phosphorylation of
AKT , a major
regulator of
GSK-3beta
Burgos-Ramos et al., J Neurochem 2009
(Calcium Signaling) :
GPE and cPG did not change Abeta25-35 levels, but GPE partially restored SRIF and SRIF receptor 2 protein content and mRNA levels and protected against cell death after Abeta25-35 insult, which was coincident with
Akt activation and
glycogen synthase kinase 3beta inhibition
Saegusa et al., Am J Pathol 2009
(Carcinosarcoma...) :
In endometrial cancer cell lines, active
Akt induced the stabilization of nuclear beta-catenin through the phosphorylation of
GSK-3beta , and this, in turn, led to the transactivation of Slug, which was mediated by nuclear beta-catenin
Hayashi et al., Thromb Haemost 2009
:
It is known that inhibition of
Akt phosphorylation
leads to inhibition of phosphorylation of
glycogen synthase kinase 3-beta ( GSK-3beta ), which is an effector of Akt, but cAMP elevating agents stimulated GSK-3beta phosphorylation at Ser9
Venkatesan et al., Cell Signal 2010
:
Further, WISP1 stimulates
PI3K-Akt dependent
GSK3beta phosphorylation and beta-catenin nuclear translocation
Becker et al., PloS one 2010
(Colitis) :
This was associated with inactivation of
glycogen synthase kinase-3beta ( GSK-3beta ) and
activation of
Akt
Kizhakkayil et al., Biochem Biophys Res Commun 2010
:
The inhibitor LY290042 was capable of attenuating curcumin induced
Akt phosphorylation and
activation of
GSK3beta
Desai et al., Hepatology 2010
(Bile Duct Diseases...) :
Hearts of DDC fed mice showed hypertrophic signaling (
activation of v-akt murine thymoma viral oncogene/protein kinase B [
AKT ], inhibition of glycogen synthase kinase-3beta
[GSK3beta ] , a 20-fold up-regulation of beta myosin heavy chain RNA and elevated G(s)alpha/G(i)alpha ratio ... Treatment of mouse cardiomyocytes ( which express the membrane bile acid receptor TGR5 ) with potent natural TGR5 agonists, taurochenodeoxycholic acid and lithocholic acid, activated
AKT and
inhibited GSK3beta , similar to the changes seen in DDC fed mouse hearts
Howard et al., J Exp Ther Oncol 2010
(Glioblastoma) :
Inhibition of EGFR signaling by AG1478 increased GSC senescence and apoptosis, likely via inhibition of
AKT and
activation of
GSK3beta
Zhou et al., Biol Psychiatry 2012
:
The response of FoxO3a is accompanied by a transient inactivation of
Akt and a prolonged
activation of
glycogen synthase kinase-3beta ( GSK3ß )
Saba et al., J Investig Med 2012
(Acquired Immunodeficiency Syndrome...) :
Protein kinase C-beta-selective inhibition was observed not to affect
AKT phosphorylation but to
induce a rapid and sustained reduction in the phosphorylation of
glycogen synthase kinase-3 beta , ribosomal protein S6, and mammalian target of rapamycin in sensitive cell lines