@prefix this: . @prefix sub: . @prefix beldoc: . @prefix rdfs: . @prefix rdf: . @prefix xsd: . @prefix dct: . @prefix dce: . @prefix pav: . @prefix np: . @prefix belv: . @prefix prov: . @prefix hgnc: . @prefix proteinModification: . @prefix psimod: . @prefix go: . @prefix Protein: . @prefix geneProductOf: . @prefix hasAgent: . @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 belv:variantOf hgnc:4617; a proteinModification:, psimod:00696 . sub:_2 hasAgent: sub:_3; a go:0016301 . sub:_3 geneProductOf: hgnc:4617; a Protein: . sub:_4 occursIn: species:9606; rdf:object sub:_2; rdf:predicate belv:directlyDecreases; rdf:subject sub:_1; a rdf:Statement . sub:assertion rdfs:label "p(HGNC:GSK3B,pmod(P,S)) =| kin(p(HGNC:GSK3B))" . } 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:_6; pav:version "1.4" . sub:_5 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:_6 rdfs:label "Selventa" . sub:assertion prov:hadPrimarySource pubmed:12097378; prov:wasDerivedFrom beldoc:, sub:_5 . } sub:pubinfo { this: dct:created "2014-07-03T14:30:04.194+02:00"^^xsd:dateTime; pav:createdBy orcid:0000-0001-6818-334X, orcid:0000-0002-1267-0234 . }