1. Catalog
  2. Nodes
  3. p(FPLX:AKT)

p(FPLX:AKT)

Equivalencies: 0 | Classes: 0 | Children: 0 | Explore

Entity

Name
AKT
Namespace
FPLX
Namespace Version
20180917
Namespace URL
https://raw.githubusercontent.com/sorgerlab/famplex/e8ae9926ff95266032cb74f77973c84939bffbeb/export/famplex.belns

Appears in Networks 11

Nicotinic acetylcholine receptor signalling: roles in Alzheimer's disease and amyloid neuroprotection. v1.0.0

Role of the nicotinic acetylcholine receptor in Alzheimer's disease pathology and treatment v1.0.1

The Biology of Proteostasis in Aging and Disease v1.0.0

Tau Modifications v1.9.5

Tau Modifications Sections of NESTOR

Anatabine Attenuates Tau Phosphorylation and Oligomerization in P301S Tau Transgenic Mice v1.0.0

Phosphatase: PP2A structural importance, regulation and its aberrant expression in cancer v1.0.0

The Spleen Tyrosine Kinase (Syk) Regulates Alzheimer Amyloid-β Production and Tau Hyperphosphorylation* v1.0.0

Nuclear Factor Kappa-light-chain-enhancer of Activated B Cells (NF-κB) - a Friend, a Foe, or a Bystander - in the Neurodegenerative Cascade and Pathogenesis of Alzheimer's Disease v1.0.0

Phytochemicals as inhibitors of NF-κB for treatment of Alzheimer’s disease v1.0.0

Upstream regulators and downstream effectors of NF-κBinAlzheimer's disease v1.0.0

mTOR-Related Brain Dysfunctions in Neuropsychiatric Disorders v1.0.0

In-Edges 23

bp(GO:"insulin receptor signaling pathway") association p(FPLX:AKT) View Subject | View Object

AKT interacts with BAD to regulate apoptosis and, interestingly, also has many interacting partners in the insulin signaling pathway. Abeta increased activity of BAD, lowered the activity of the antiapoptotic protein BCL2, in rat hippocampal neurons in primary culture (Koriyama et al., 2003) and has been shown to be toxic to human neuroblastoma cells by increasing BAX activity and decreasing BCl-2 activity (Clementi et al., 2006). PubMed:19293145

Appears in Networks:

complex(p(FPLX:AKT), p(HGNC:AGAP2)) hasComponent p(FPLX:AKT) View Subject | View Object

Appears in Networks:

complex(p(FPLX:AKT), p(HGNC:AGAP2)) increases act(p(FPLX:AKT)) View Subject | View Object

In a microarray study comparing brains from patients with AD with control brains, FYN was found to be significantly upregulated in AD (Wang et al., 2003a). In this context, it is of interest that FYN has also been shown to activate the PI3K/AKT cascade, thereby inhibiting apoptosis (Tang et al., 2007). Indeed, FYN is required for phos- phorylation of phosphoinositide 3-kinase enhancer (PIKE), which itself regulates AKT (Fig. 3). PIKE binds to AKT and up-regulates its kinase a ctivity, thereby reducing apoptosis. Phosphorylation protects PIKE from caspase cleavage, hence FYN is antiapoptotic (Tang et al., 2007). PubMed:19293145

Appears in Networks:

complex(p(FPLX:AKT), p(HGNC:BAD)) hasComponent p(FPLX:AKT) View Subject | View Object

Appears in Networks:

a(CHEBI:"(-)-cotinine") increases act(p(FPLX:AKT)) View Subject | View Object

In a mouse model of AD, cotinine treatment decreased the plaque load and was able to activate the Akt pathway, that was shown to be neuroprotective (Echeverria et al., 2011) PubMed:25514383

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(PUBCHEM:10521421) decreases act(p(FPLX:AKT)) View Subject | View Object

An in silico screen based on the structure of 10-NCP, an Akt inhibitor that potently induces autophagy (144), identified the molecules FPZ and MTM as potent activators of autophagic flux and clearance of TDP-43 in mammalian cells (145). PubMed:25784053

Appears in Networks:
Annotations
Cell Ontology (CL)
motor neuron

p(FPLX:AKT, pmod(Ph, Ser, 473)) increases act(p(FPLX:AKT)) View Subject | View Object

GSK3β is inactivated upon phosphorylation of Ser9 by protein kinase B (AKT) [41] whereas AKT phosphorylation at Ser473 results in AKT activation [42]. DOI:10.4172/2168-975X.1000126

Appears in Networks:

p(HGNC:NFE2L2) positiveCorrelation p(FPLX:AKT) View Subject | View Object

The second mechanism is related to GSK-3, which phosphorylates NRF2 creating a recognition site for β-Transducin Repeat Containing E3 Ubiquitin Protein Ligase (β-TrCP). β-TrCP leads to Cullin-1/Rbx1-mediated NRF2 ubiquitination and its subsequent degradation [8]. Since GSK-3β is inhibited by phosphorylation at Ser9 by Ser/Thr protein kinases such as AKT, it has been suggested that NRF2 might be up-regulated through activation of AKT and permanent inactivation of GSK-3 [9], [10]. PubMed:29121589

Appears in Networks:

p(FPLX:AKT, pmod(Ph, Ser, 473)) increases act(p(FPLX:AKT)) View Subject | View Object

Wild-type MEFs treated with DMF (20 μM) showed a time-dependent response effect activating phosphorylation of ERK (Fig. 2A, B) and p38 (Fig. 2A, C), that was maximal within 5 min. The Ser/Thr protein kinase AKT, an upstream regulator of GSK-3β, was also activated after 5 min as determined by increased phosphorylation of S473 (Fig. 2A, D) PubMed:29121589

Appears in Networks:

p(FPLX:AKT, pmod(Ph, Ser, 473)) increases act(p(FPLX:AKT)) View Subject | View Object

Phosphorylation at Thr-308 and Ser-473 leads to activation of Akt and it was found that deregulation of Akt is associated with various human malignancies. PubMed:23454242

Appears in Networks:

p(FPLX:AKT, pmod(Ph, Thr, 308)) increases act(p(FPLX:AKT)) View Subject | View Object

Phosphorylation at Thr-308 and Ser-473 leads to activation of Akt and it was found that deregulation of Akt is associated with various human malignancies. PubMed:23454242

Appears in Networks:

bp(GO:"calcium ion import") increases act(p(FPLX:AKT)) View Subject | View Object

In addition to CamKII, other kinases activated in response to a rise in cytosolic Ca2+ such as protein kinase C (PKC), phosphatidylinositol-3-kinase (PI3K), and Akt, also activate NF-κB signaling pathway by increasing the phosphorylation and activation of IKK PubMed:28745240

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

a(CHEBI:berberine) decreases act(p(FPLX:AKT)) View Subject | View Object

Berberine inhibited the p38,ERK and Akt signaling pathways, which were stimulated by A PubMed:29179999

Appears in Networks:

a(CHEBI:methamphetamine) increases act(p(FPLX:AKT)) View Subject | View Object

Likewise, administration of either D1R agonists or METH enhances Akt activity and over-activates mTOR signaling PubMed:30061532

Appears in Networks:

complex(p(FPLX:AKT), p(HGNC:CCDC88A)) hasComponent p(FPLX:AKT) View Subject | View Object

Appears in Networks:

complex(p(FPLX:AKT), p(HGNC:CCDC88A)) increases act(p(FPLX:AKT)) View Subject | View Object

In particular, DISC1 acts by blocking KIAA1212, an Akt-binding partner, which directly interacts with Akt and strengthens the activation of this kinase, which represents a major mediator of the mTOR pathway. PubMed:30061532

Appears in Networks:

p(HGNC:CCDC88A) increases act(p(FPLX:AKT)) View Subject | View Object

Therefore, the binding between DISC1 and KIAA1212 prevents KIAA1212-dependent Akt activation (Figure 3). PubMed:30061532

Appears in Networks:

act(p(FPLX:PI3K)) increases act(p(FPLX:AKT)) View Subject | View Object

The binding between ErbB4 and PI3K activates this latter kinase, which in turn can phosphorylate and activate its downstream target Akt PubMed:30061532

Appears in Networks:

complex(p(HGNC:CCDC88A), p(HGNC:DISC1)) decreases act(p(FPLX:AKT)) View Subject | View Object

Therefore, the binding between DISC1 and KIAA1212 prevents KIAA1212-dependent Akt activation (Figure 3). PubMed:30061532

Appears in Networks:

complex(p(HGNC:CCDC88A), p(HGNC:DISC1)) decreases act(p(FPLX:AKT)) View Subject | View Object

This decreases Akt activity, which in turn dampens mTOR signaling PubMed:30061532

Appears in Networks:

p(HGNC:DISC1, var("?")) increases act(p(FPLX:AKT)) View Subject | View Object

Therefore, disruption of DISC1 activity, due to genetic rearrangements (i.e., balanced (1;11) (q42;q14) chromosomal translocation) or missense mutations, produces schizophrenic-like behavior, which is bound to enhanced Akt activity, over-activation of mTOR signaling, and depressed autophagy PubMed:30061532

Appears in Networks:

act(p(HGNC:DRD1)) increases act(p(FPLX:AKT)) View Subject | View Object

Likewise, administration of either D1R agonists or METH enhances Akt activity and over-activates mTOR signaling PubMed:30061532

Appears in Networks:

path(MESH:Schizophrenia) decreases p(FPLX:AKT) View Subject | View Object

Dysregulation in Akt signaling and altered Akt protein levels were found in the frontal cortex and hippocampus of post-mortem brain samples from individuals affected by schizophrenia PubMed:30061532

Appears in Networks:
Annotations
MeSH
Hippocampus
MeSH
Prefrontal Cortex

Out-Edges 18

p(FPLX:AKT) hasVariant p(FPLX:AKT, pmod(Ph)) View Subject | View Object

Appears in Networks:

act(p(FPLX:AKT)) decreases bp(GO:"apoptotic process") View Subject | View Object

In a microarray study comparing brains from patients with AD with control brains, FYN was found to be significantly upregulated in AD (Wang et al., 2003a). In this context, it is of interest that FYN has also been shown to activate the PI3K/AKT cascade, thereby inhibiting apoptosis (Tang et al., 2007). Indeed, FYN is required for phos- phorylation of phosphoinositide 3-kinase enhancer (PIKE), which itself regulates AKT (Fig. 3). PIKE binds to AKT and up-regulates its kinase a ctivity, thereby reducing apoptosis. Phosphorylation protects PIKE from caspase cleavage, hence FYN is antiapoptotic (Tang et al., 2007). PubMed:19293145

Appears in Networks:

p(FPLX:AKT) association bp(GO:"insulin receptor signaling pathway") View Subject | View Object

AKT interacts with BAD to regulate apoptosis and, interestingly, also has many interacting partners in the insulin signaling pathway. Abeta increased activity of BAD, lowered the activity of the antiapoptotic protein BCL2, in rat hippocampal neurons in primary culture (Koriyama et al., 2003) and has been shown to be toxic to human neuroblastoma cells by increasing BAX activity and decreasing BCl-2 activity (Clementi et al., 2006). PubMed:19293145

Appears in Networks:

p(FPLX:AKT) hasVariant p(FPLX:AKT, pmod(Ph, Thr, 308)) View Subject | View Object

Appears in Networks:

p(FPLX:AKT) regulates bp(GO:"cell growth") View Subject | View Object

Akt plays an important role in cell growth, proliferation and apoptosis. PubMed:23454242

Appears in Networks:

p(FPLX:AKT) regulates bp(GO:"cell population proliferation") View Subject | View Object

Akt plays an important role in cell growth, proliferation and apoptosis. PubMed:23454242

Appears in Networks:

p(FPLX:AKT) regulates bp(GO:"apoptotic process") View Subject | View Object

Akt plays an important role in cell growth, proliferation and apoptosis. PubMed:23454242

Appears in Networks:

act(p(FPLX:AKT)) decreases bp(HP:Neurodegeneration) View Subject | View Object

In a mouse model of AD, cotinine treatment decreased the plaque load and was able to activate the Akt pathway, that was shown to be neuroprotective (Echeverria et al., 2011) PubMed:25514383

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

p(FPLX:AKT) directlyIncreases p(HGNC:GSK3B, pmod(Ph, Ser, 9)) View Subject | View Object

GSK3β is inactivated upon phosphorylation of Ser9 by protein kinase B (AKT) [41] whereas AKT phosphorylation at Ser473 results in AKT activation [42]. DOI:10.4172/2168-975X.1000126

Appears in Networks:

p(FPLX:AKT) hasVariant p(FPLX:AKT, pmod(Ph, Ser, 473)) View Subject | View Object

Appears in Networks:

p(FPLX:AKT) increases p(HGNC:GSK3B, pmod(Ph, Ser, 9)) View Subject | View Object

The second mechanism is related to GSK-3, which phosphorylates NRF2 creating a recognition site for β-Transducin Repeat Containing E3 Ubiquitin Protein Ligase (β-TrCP). β-TrCP leads to Cullin-1/Rbx1-mediated NRF2 ubiquitination and its subsequent degradation [8]. Since GSK-3β is inhibited by phosphorylation at Ser9 by Ser/Thr protein kinases such as AKT, it has been suggested that NRF2 might be up-regulated through activation of AKT and permanent inactivation of GSK-3 [9], [10]. PubMed:29121589

Appears in Networks:

p(FPLX:AKT) positiveCorrelation p(HGNC:NFE2L2) View Subject | View Object

The second mechanism is related to GSK-3, which phosphorylates NRF2 creating a recognition site for β-Transducin Repeat Containing E3 Ubiquitin Protein Ligase (β-TrCP). β-TrCP leads to Cullin-1/Rbx1-mediated NRF2 ubiquitination and its subsequent degradation [8]. Since GSK-3β is inhibited by phosphorylation at Ser9 by Ser/Thr protein kinases such as AKT, it has been suggested that NRF2 might be up-regulated through activation of AKT and permanent inactivation of GSK-3 [9], [10]. PubMed:29121589

Appears in Networks:

p(FPLX:AKT) regulates p(HGNC:GSK3B, pmod(Ph, Ser, 9)) View Subject | View Object

GSK3β phosphorylation at Ser-9 has been shown to be mediated by PKA and AKT (protein kinase B) (57, 58). PubMed:25331948

Appears in Networks:

act(p(FPLX:AKT)) increases act(complex(GO:"NF-kappaB complex")) View Subject | View Object

In addition to CamKII, other kinases activated in response to a rise in cytosolic Ca2+ such as protein kinase C (PKC), phosphatidylinositol-3-kinase (PI3K), and Akt, also activate NF-κB signaling pathway by increasing the phosphorylation and activation of IKK PubMed:28745240

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

act(p(FPLX:AKT)) increases act(complex(GO:"IkappaB kinase complex")) View Subject | View Object

In addition to CamKII, other kinases activated in response to a rise in cytosolic Ca2+ such as protein kinase C (PKC), phosphatidylinositol-3-kinase (PI3K), and Akt, also activate NF-κB signaling pathway by increasing the phosphorylation and activation of IKK PubMed:28745240

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

act(p(FPLX:AKT)) increases p(MESH:"I-kappa B Kinase", pmod(Ph)) View Subject | View Object

In addition to CamKII, other kinases activated in response to a rise in cytosolic Ca2+ such as protein kinase C (PKC), phosphatidylinositol-3-kinase (PI3K), and Akt, also activate NF-κB signaling pathway by increasing the phosphorylation and activation of IKK PubMed:28745240

Appears in Networks:
Annotations
MeSH
Alzheimer Disease

act(p(FPLX:AKT)) increases p(HGNC:RELA) View Subject | View Object

Activation of AKT augments the transactivating activity and produces higher nuclear levels of p65-NF- κB, which is important for neuroprotection. PubMed:27288790

Appears in Networks:

p(FPLX:AKT) regulates act(p(HGNC:MTOR)) View Subject | View Object

In particular, DISC1 acts by blocking KIAA1212, an Akt-binding partner, which directly interacts with Akt and strengthens the activation of this kinase, which represents a major mediator of the mTOR pathway. PubMed:30061532

Appears in Networks:

About

BEL Commons is developed and maintained in an academic capacity by Charles Tapley Hoyt and Daniel Domingo-Fernández at the Fraunhofer SCAI Department of Bioinformatics with support from the IMI project, AETIONOMY. It is built on top of PyBEL, an open source project. Please feel free to contact us here to give us feedback or report any issues. Also, see our Publishing Notes and Data Protection information.

If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.