◀ Back to AKT1
AKT1 — HSP90AA1
Pathways - manually collected, often from reviews:
-
NCI Pathway Database Signaling events mediated by VEGFR1 and VEGFR2:
AKT1 (AKT1)
→
eNOS/Hsp90 complex (NOS3-HSP90AA1)
(modification, activates)
Fulton et al., Nature 1999, Dimmeler et al., Nature 1999, Brouet et al., J Biol Chem 2001*
Evidence: assay
-
NCI Pathway Database Regulation of Telomerase:
Telomerase complex (TERT-PTGES3)
→
Telomerase/AKT1/mTOR/p70S6K complex (AKT1-MTOR-RPS6KB1-HSP90AA1-TERT-PTGES3-DKC1)
(modification, collaborate)
Haendeler et al., FEBS Lett 2003
Evidence: assay
-
NCI Pathway Database Regulation of Telomerase:
Telomerase/AKT1/mTOR/p70S6K complex (AKT1-MTOR-RPS6KB1-HSP90AA1-TERT-PTGES3-DKC1)
→
AKT1 (AKT1)
(modification, collaborate)
Haendeler et al., FEBS Lett 2003
Evidence: assay
-
NCI Pathway Database Regulation of Telomerase:
Telomerase/AKT1/mTOR/p70S6K complex (AKT1-MTOR-RPS6KB1-HSP90AA1-TERT-PTGES3-DKC1)
→
p70S6K (RPS6KB1)
(modification, collaborate)
Haendeler et al., FEBS Lett 2003
Evidence: assay
-
NCI Pathway Database Regulation of Telomerase:
Telomerase/AKT1/mTOR/p70S6K complex (AKT1-MTOR-RPS6KB1-HSP90AA1-TERT-PTGES3-DKC1)
→
mTOR (MTOR)
(modification, collaborate)
Haendeler et al., FEBS Lett 2003
Evidence: assay
-
NCI Pathway Database IL2 signaling events mediated by PI3K:
TERT (TERT)
→
AKT1/mTOR/p70S6K/Hsp90/TERT complex (AKT1-MTOR-RPS6KB1-HSP90AA1-TERT)
(modification, collaborate)
Kawauchi et al., J Immunol 2005
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database IL2 signaling events mediated by PI3K:
Hsp90 (HSP90AA1)
→
AKT1 (AKT1)
(modification, collaborate)
Kawauchi et al., J Immunol 2005
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database IL2 signaling events mediated by PI3K:
Hsp90 (HSP90AA1)
→
AKT1/mTOR/p70S6K/Hsp90/TERT complex (AKT1-MTOR-RPS6KB1-HSP90AA1-TERT)
(modification, collaborate)
Kawauchi et al., J Immunol 2005
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database IL2 signaling events mediated by PI3K:
AKT1 (AKT1)
→
AKT1/mTOR/p70S6K/Hsp90/TERT complex (AKT1-MTOR-RPS6KB1-HSP90AA1-TERT)
(modification, collaborate)
Kawauchi et al., J Immunol 2005
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database IL2 signaling events mediated by PI3K:
AKT1/mTOR/p70S6K/Hsp90/TERT complex (AKT1-MTOR-RPS6KB1-HSP90AA1-TERT)
→
mTOR (MTOR)
(modification, collaborate)
Kawauchi et al., J Immunol 2005
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database IL2 signaling events mediated by PI3K:
AKT1/mTOR/p70S6K/Hsp90/TERT complex (AKT1-MTOR-RPS6KB1-HSP90AA1-TERT)
→
p70S6K (RPS6KB1)
(modification, collaborate)
Kawauchi et al., J Immunol 2005
Evidence: mutant phenotype, assay, physical interaction
-
NCI Pathway Database VEGFR1 specific signals:
AKT1 (AKT1)
→
eNOS/Hsp90 complex (NOS3-HSP90AA1)
(translocation, activates)
Fulton et al., Nature 1999, Dimmeler et al., Nature 1999, Dimmeler et al., FEBS Lett 2000, Urbich et al., FASEB J 2002, Michell et al., J Biol Chem 2002, Mount et al., J Mol Cell Cardiol 2007
Evidence: assay
-
Reactome Reaction:
HSP90AA1
→
AKT1
(direct_complex)
Fulton et al., Nature 1999, Dimmeler et al., Nature 1999, Michell et al., Curr Biol 1999*, Vásquez-Vivar et al., Biochem J 2002*, Berka et al., Biochemistry 2004*
-
Reactome Reaction:
HSP90AA1
→
AKT1
(indirect_complex)
Fontana et al., Circ Res 2002*, Takahashi et al., J Biol Chem 2003*
-
Reactome Reaction:
HSP90AA1
→
AKT1
(reaction)
Fontana et al., Circ Res 2002*, Takahashi et al., J Biol Chem 2003*
Protein-Protein interactions - manually collected from original source literature:
Studies that report less than 10 interactions are marked with *
-
IRef Biogrid Interaction:
AKT1
—
HSP90AA1
(physical association, affinity chromatography technology)
Klein et al., J Biol Chem 2005
-
IRef Biogrid Interaction:
AKT1
—
HSP90AA1
(physical association, affinity chromatography technology)
Haendeler et al., FEBS Lett 2003
-
IRef Biogrid Interaction:
AKT1
—
HSP90AA1
(physical association, affinity chromatography technology)
Kawauchi et al., J Immunol 2005
-
IRef Biogrid Interaction:
AKT1
—
HSP90AA1
(physical association, affinity chromatography technology)
Sato et al., Proc Natl Acad Sci U S A 2000*
-
IRef Biogrid Interaction:
AKT1
—
HSP90AA1
(physical association, affinity chromatography technology)
Basso et al., J Biol Chem 2002*
-
IRef Biogrid Interaction:
AKT1
—
HSP90AA1
(physical association, affinity chromatography technology)
Su et al., Cell Signal 2011*
-
MIPS CORUM eNOS-HSP90-AKT complex, VEGF induced:
eNOS-HSP90-AKT complex, VEGF induced complex (AKT1-HSP90AA1-NOS3)
Brouet et al., J Biol Chem 2001*
-
IRef Corum Interaction:
Complex of HSP90AA1-NOS3-AKT1
(association, anti bait coimmunoprecipitation)
Brouet et al., J Biol Chem 2001*
-
IRef Dip Interaction:
Complex of STUB1-AKT1-HSP90AA1
(anti tag coimmunoprecipitation)
Dickey et al., Proc Natl Acad Sci U S A 2008
-
IRef Hprd Interaction:
AKT1
—
HSP90AA1
(in vivo)
Sato et al., Proc Natl Acad Sci U S A 2000*, Kim et al., Eur J Pharmacol 2009*
-
IRef Hprd Interaction:
Complex of HSP90AA1-AKT1-AKT1-HSP90AA1-HSP90AA1-AKT1
(in vivo)
Basso et al., J Biol Chem 2002*
-
IRef Innatedb Interaction:
AKT1
—
HSP90AA1
(unknown, -)
Sato et al., Proc Natl Acad Sci U S A 2000*
-
IRef Intact Interaction:
Complex of AKT1-HSP90AA1-CDC37
(association, coimmunoprecipitation)
Basso et al., J Biol Chem 2002*
-
IRef Ophid Interaction:
AKT1
—
HSP90AA1
(aggregation, confirmational text mining)
Sato et al., Proc Natl Acad Sci U S A 2000*
-
IRef Ophid Interaction:
AKT1
—
HSP90AA1
(aggregation, interologs mapping)
Brown et al., Bioinformatics 2005
Text-mined interactions from Literome
Fujita et al., J Biol Chem 2002
:
Screening of drugs that could interfere with the Akt signaling pathway revealed that
Hsp90 inhibitors ( e.g. geldanamycin, radicicol, and its analogues )
induced Akt dephosphorylation, which resulted in Akt inactivation and apoptosis of the cells ...
Hsp90 inhibitors did not directly
affect Akt kinase activity in vitro
Basso et al., J Biol Chem 2002
:
Functional
Hsp90 is
required for the stability of
Akt in the complex
Solit et al., Cancer Res 2003
(Breast Neoplasms) :
These results suggest that
Hsp90 inhibitors can effectively
suppress Akt activity in animal models of human cancer at nontoxic doses, thus sensitizing tumor cells to proapoptotic stimuli
Takahashi et al., J Biol Chem 2003
:
Akt was not observed in the eNOS complex in the absence of HSP90, but both active and inactive
Akt associated with eNOS in the
presence of
HSP90
Fujita et al., Cancer Chemother Pharmacol 2003
:
HSP90 inhibitors and topotecan
suppressed AKT activity via indirectly downregulating PDK1 and phosphatidylinositide-3-OH kinase activities
Xu et al., Cancer Res 2003
(Breast Neoplasms) :
Decreased AKT phosphorylation is not due to blockade of AKT activation or to preferential
HSP90 mediated degradation of phosphorylated
AKT
Yun et al., Cell Signal 2005
:
In this report, we have examined the
role of
Hsp90 in regulating the activity of
Akt in differentiating C2C12 myoblasts
Koga et al., Proc Natl Acad Sci U S A 2006
:
Hsp90 inhibition transiently activates Src kinase and
promotes Src dependent
Akt and Erk activation
Boehm et al., Arthritis Rheum 2007
:
Inhibition of
Hsp90 with 100 nM or 500 nM geldanamycin
blocked IGF-1 induced cell proliferation,
Akt and p42/44 activation, and COL2A1 expression
Zhao et al., Zhonghua Shao Shang Za Zhi 2007
(Disease Models, Animal) :
Endogenous
HSP90 plays important roles in maintaining the cardiomyocyte activity, and its level might
affect the expression of
AKT
Hemdan et al., J Neurochem 2008
:
The
HSP-90 inhibitor
caused a decrease in
P-Akt level, induced caspase-3 activation, increased nuclear condensation and caused a loss in cell viability
Babchia et al., Invest Ophthalmol Vis Sci 2008
(Melanoma...) :
HSP90 inhibition also
reduced the expression of
Akt , but the inhibition of Akt had no effect on cell proliferation, ruling out a role of Akt in the 17-AAG induced inhibition of cell proliferation
Kabakov et al., Int J Radiat Oncol Biol Phys 2008
:
The drug induced radiosensitization of ECs seems to be caused by prevention of
Hsp90 dependent phosphorylation ( activation ) of
Akt that results in blocking the radioprotective phosphatidylinositol 3-kinase/Akt pathway
Yano et al., Proc Natl Acad Sci U S A 2008
(Bone Neoplasms...) :
Hsp90 inhibition transiently activates osteoclast Src kinase and
promotes Src dependent
Akt activation
Barksdale et al., J Neurochem 2009
(Neuroblastoma) :
We have found that
HSP90 is
responsible for
Akt accumulation in the mitochondria in unstimulated cells ... These results indicate that the level of
Akt in the mitochondria is
dependent on
HSP90 chaperoning activity and that Akt import can cause dynamic changes in mitochondrial configuration
Ram et al., Clin Cancer Res 2009
(Neoplasms) :
Telomerase was
activated by phosphorylation by
Akt and by cytoplasmic-nuclear shift
Hackl et al., Surgery 2010
(Acute Disease...) :
Inhibition of
HSP90 effectively
diminished the constitutive phosphorylation of
Akt , Erk, and STAT3 in PHHs. Conversely, inhibition of HSP90 significantly increased the expression of both VEGF and HGF mRNA, and induced HSP70 protein in PHH cultures in vitro
Bhat et al., Mol Immunol 2010
:
Our results demonstrate that binding of CpG ODN ( 2007 ) to
Hsp90 induces activation of ERK2 and
AKT phosphorylation leading to the production of high levels of IFN-gamma, IL-6, MIP-3alpha and nitric oxide ( NO )
Liao et al., American journal of translational research 2010
:
Reports on ubiquitin dependent Akt degradation, caspase dependent cleavage, and the
roles of molecular chaperone
heat shock protein 90 (Hsp90) in the regulation of
Akt stability are summarized
Redlak et al., Dig Dis Sci 2011
(Stomach Neoplasms) :
The binding of
HSP90 with pro-survival kinase Akt
prevents proteosomal degradation of
Akt and contributes to the functional stabilization of PI3K/Akt signaling and cell survival
Bai et al., Apoptosis 2011
(Liver Neoplasms...) :
However,
Hsp90 inhibitors effectively blocked SMC3 induced NF-?B activation through degradation of RIP1 and IKKß, two key components of the NF-?B activation pathway, and
reduced both the constitutive and SMC3 induced
Akt activity through degradation of the Akt protein
Tramentozzi et al., J Cell Mol Med 2011
:
Results reveal a fundamental
role of
HSP90 in the
PI3K/Akt pathway mediated angiogenic-like effect of Grp94-IgG, also questioning the capacity of CTT to serve as an effective inhibitor of the angiogenic effect
Khan et al., Mol Carcinog 2012
:
It
inhibited phosphatidylinositol-3-kinase
(PI3K)/AKT activity, NF-?B,
Hsp-90 , and survivin which may enhance the sensitivity of cells to apoptosis
Sobhan et al., Cancer Lett 2012
:
Hsp90 inhibitors
induced down regulation of
Akt leading to proteasomal degradation of survivin and consequent mitochondrial apoptosis
Yoshida et al., Cell cycle (Georgetown, Tex.) 2011
(Urinary Bladder Neoplasms) :
We also showed that CRT induces accumulation of nuclear
phospho-Akt , which antagonizes apoptosis, and that
Hsp90 inhibitors
block the cellular process
Halder et al., FEBS J 2012
:
Inhibition of upstream
Hsp90 by TF and TR consequently
attenuated Akt signaling and reduced the level of CDK2
Flandrin-Gresta et al., Oncotarget 2012
(Cell Transformation, Neoplastic...) :
In conclusion, our data suggest the implication of
HSP90 and FAK and
AKT activation in the pathogenesis of myelodysplastic syndromes with excess of blasts and evolution to leukaemia
Kasukabe et al., Int J Oncol 2013
:
We also found that the
HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin ( 17-AAG ) or arsenic trioxide ( ATO ) in combination with rapamycin markedly inhibited the growth of MCF-7 cells and 17-AAG or ATO
suppressed rapamycin induced phosphorylation of
Akt
Zhang et al., BMB Rep 2013
:
Further study showed that
Akt phosphorylation was
enhanced by
Hsp90ß , which was not due to the activation of upstream PI3K and PDK1 but because of stabilization of pAkt via direct interaction between Hsp90ß and pAkt
Leonard et al., Cell cycle (Georgetown, Tex.) 2013
:
Inhibition of
Akt activation with MK2206
reduced the whole-cell and
centrosome levels of PLK-1 and ?-tubulin and also prevented the recruitment of PTEN to mitotic centrosomes
Su et al., Arch Biochem Biophys 2013
:
Hsp90 inhibition
causes Akt degradation, but the mechanism remains unclear
Wang et al., Chem Biol Interact 2013
:
The
Hsp90 inhibitor SNX-2112,
induces apoptosis in multidrug resistant K562/ADR cells through suppression of
Akt/NF-?B and disruption of mitochondria dependent pathways