General Information:

Id: 861
Diseases: Alzheimer disease - [OMIM]
Homo sapiens
brain
article
Reference: Pei JJ et al.(2003) Role of protein kinase B in Alzheimers neurofibrillary pathology. Acta Neuropathol. 105: 381-392 [PMID: 12624792]

Interaction Information:

Comment Protein kinase B (PKB) is an important intermediate in the phosphatidylinositol-3 kinase signaling cascade that acts to phosphorylate glycogen synthase kinase-3 (GSK-3) at its serine 9 residue, thereby inactivating it.
Formal Description
Interaction-ID: 5106

gene/protein

AKT1

increases_phosphorylation of

gene/protein

GSK3B

at Ser9, thereby inactivating GSK3B;
Drugbank entries Show/Hide entries for AKT1 or GSK3B
Comment PKB was increased in AD brains as compared with normal aged and Huntington's disease controls.
Formal Description
Interaction-ID: 5108

increases_quantity of

gene/protein

AKT1

Drugbank entries Show/Hide entries for AKT1
Comment This increase in PKB levels corresponded with a several-fold increase in the levels of total tau and abnormally hyperphosphorylated tau at the Tau-1 site.
Formal Description
Interaction-ID: 5109

phenotype

increased AKT1 level

cooccurs with

phenotype

increased MAPT level

Comment This increase in PKB levels corresponded with a several-fold increase in the levels of total tau and abnormally hyperphosphorylated tau at the Tau-1 site.
Formal Description
Interaction-ID: 5111

phenotype

increased AKT1 level

cooccurs with

phenotype

increased MAPT-phos level

There is an increase of abnormally hyperphosphorylated tau at the Tau-1 site.
Comment The amount of activated PKB (phos-Thr308) is increased in correlation to the neurofibrillary changes.
Formal Description
Interaction-ID: 5115

phenotype

increased AKT-phosThr308 level

cooccurs with

Comment Protein kinase B (PKB) is an important intermediate in the phosphatidylinositol-3 kinase signaling cascade that acts to phosphorylate glycogen synthase kinase-3 (GSK-3) at its serine 9 residue, thereby inactivating it.
Formal Description
Interaction-ID: 5117

gene/protein

AKT1

affects_phosphorylation of

gene/protein

GSK3

at Ser9; this phosphorylated GSK3 is inactivated
Drugbank entries Show/Hide entries for AKT1
Comment Both active PKB and GSK-3alpha/beta preceded the abnormal hyperphosphorylation of tau in pattern 1 neurons.
Formal Description
Interaction-ID: 5119

gene/protein

AKT1

increases_quantity of

protein modification

MAPT-hyperphos

Drugbank entries Show/Hide entries for AKT1
Comment Hypothesis: Like JNK and p38, ERK1/2, and cdc2, PKB activation and accumulation of p-Tyr GSK-3alpha/beta could be early events involved in the pathogenesis of AD neurofibrillary changes.
Formal Description
Interaction-ID: 5120

none selected

Drugbank entries Show/Hide entries for or
Comment Hypothesis: In AD, the reduced PTP-1B activity may fail to counter-balance the overactive fyn kinase that phosphorylates GSK-3beta at Tyr216. Consequently, to neutralize the effect of accumulated GSK-3, more PKB is likely synthesized and phosphorylated by 3-phosphoinositide-dependent protein kinase 1 (PDK1) that may be constitutively active under basal conditions.
Formal Description
Interaction-ID: 5121

none selected

Drugbank entries Show/Hide entries for or
Comment Hypothesis: It is likely that once neurons develop neurofibrillary degeneration by GSK-3alpha/beta activation, apoptosis may be inhibited by overactivation of PKB.
Formal Description
Interaction-ID: 5122

none selected

Drugbank entries Show/Hide entries for or
Comment In the protein kinase B signaling cascade (=Akt signaling pathway) AKT1 acts as key enzyme.
Formal Description
Interaction-ID: 19094

gene/protein

AKT1

affects_activity of

Drugbank entries Show/Hide entries for AKT1
Comment Both active PKB and GSK-3alpha/beta preceded the abnormal hyperphosphorylation of tau in pattern 1 neurons.
Formal Description
Interaction-ID: 23597

gene/protein

GSK3B

increases_quantity of

protein modification

MAPT-hyperphos

Drugbank entries Show/Hide entries for GSK3B
Comment Both active PKB and GSK-3alpha/beta preceded the abnormal hyperphosphorylation of tau in pattern 1 neurons.
Formal Description
Interaction-ID: 23598

gene/protein

GSK3A

increases_quantity of

protein modification

MAPT-hyperphos