@prefix dcterms: .
@prefix this: .
@prefix sub: .
@prefix beldoc: .
@prefix rdfs: .
@prefix rdf: .
@prefix xsd: .
@prefix dce: .
@prefix pav: .
@prefix np: .
@prefix belv: .
@prefix prov: .
@prefix go: .
@prefix Protein: .
@prefix hgnc: .
@prefix geneProductOf: .
@prefix hasAgent: .
@prefix mesh: .
@prefix species: .
@prefix occursIn: .
@prefix pubmed: .
@prefix orcid: .
sub:Head {
this: np:hasAssertion sub:assertion;
np:hasProvenance sub:provenance;
np:hasPublicationInfo sub:pubinfo;
a np:Nanopublication .
}
sub:assertion {
sub:_1 hasAgent: sub:_2;
a go:0016301 .
sub:_2 geneProductOf: hgnc:4617;
a Protein: .
sub:_3 belv:translocationFrom mesh:D003593;
belv:translocationOf sub:_4;
belv:translocationTo mesh:D002467 .
sub:_4 geneProductOf: hgnc:2514;
a Protein: .
sub:_5 occursIn: species:9606;
rdf:object sub:_3;
rdf:predicate belv:decreases;
rdf:subject sub:_1;
a rdf:Statement .
sub:assertion rdfs:label "kin(p(HGNC:GSK3B)) -| tloc(p(HGNC:CTNNB1),MESHCS:Cytoplasm,MESHCS:\"Cell Nucleus\")" .
}
sub:provenance {
beldoc: dce:description "Approximately 61,000 statements.";
dce:rights "Copyright (c) 2011-2012, Selventa. All rights reserved.";
dce:title "BEL Framework Large Corpus Document";
pav:authoredBy sub:_7;
pav:version "20131211" .
sub:_6 prov:value "Beta-catenin is a transcriptional activator that is regulated by glycogen synthase kinase-3 (GSK-3). GSK-3 is constitutively active in unstimulated cells where it phosphorylates beta-catenin, targeting beta-catenin for rapid degradation. Receptor-induced inhibition of GSK-3 allows beta-catenin to accumulate in the cytoplasm and then translocate to the nucleus where it promotes the transcription of genes such as c-myc and cyclin D1. Wnt hormones, the best known regulators of beta-catenin, inhibit GSK-3 via the Disheveled protein. However, GSK-3 is also inhibited when it is phosphorylated by Akt, a downstream target of phosphatidylinositol 3-kinase (PI3K). We have previously shown that B cell Ag receptor (BCR) signaling leads to activation of PI3K and Akt as well as inhibition of GSK-3. Therefore, we hypothesized that BCR engagement would induce the accumulation of beta-catenin via a PI3K/Akt/GSK-3 pathway. We now show that BCR ligation causes an increase in the level of beta-catenin in the nuclear fraction of B cells as well as an increase in beta-catenin-dependent transcription. Direct inhibition of GSK-3 by LiCl also increased beta-catenin levels in B cells. This suggests that GSK-3 keeps beta-catenin levels low in unstimulated B cells and that BCR-induced inhibition of GSK-3 allows the accumulation of beta-catenin. Surprisingly, we found that the BCR-induced phosphorylation of GSK-3 on its negative regulatory sites, as well as the subsequent up-regulation of beta-catenin, was not mediated by Akt but by the phospholipase C-dependent activation of protein kinase C. Thus, the BCR regulates beta-catenin levels via a phospholipase C/protein kinase C/GSK-3 pathway.";
prov:wasQuotedFrom pubmed:12097378 .
sub:_7 rdfs:label "Selventa" .
sub:assertion prov:hadPrimarySource pubmed:12097378;
prov:wasDerivedFrom beldoc:, sub:_6 .
}
sub:pubinfo {
this: dcterms:created "2014-07-03T14:31:51.374+02:00"^^xsd:dateTime;
pav:createdBy orcid:0000-0001-6818-334X, orcid:0000-0002-1267-0234 .
}