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dc.contributor.authorOrme, MH
dc.contributor.authorGiannini, AL
dc.contributor.authorVivanco, MD
dc.contributor.authorKypta, RM
dc.date.accessioned2018-09-12T11:43:54Z
dc.date.issued2003
dc.identifier3
dc.identifier.citationMolecular and Cellular Neuroscience, 2003, 24 pp. 673 - 686
dc.identifier.issn1044-7431
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2650
dc.identifier.doi10.1016/S1044-7431(03)00229-X
dc.description.abstractWe have sought to determine the roles of β-catenin and the Wnt signaling pathway in neurite outgrowth using a model cell system, the Neuro-2a neuroblastoma cell line. Activation of the Wnt signaling pathway disrupts a multiprotein complex that includes β-catenin, Axin, and glycogen synthase kinase-3 (GSK-3), which would otherwise promote the phosphorylation and degradation of β-catenin. Stabilized β-catenin accumulates in the cytosol and in the nucleus; in the nucleus it binds to TCF family transcription factors, forming a bipartite transcriptional activator of Wnt target genes. These events can be mimicked by lithium (Li+), which inhibits GSK-3 activity. Both Li+ and the GSK-3 inhibitor SB415286 induced neurite outgrowth of Neuro-2a cells. Li+-induced neurite outgrowth did not require β-catenin-/TCF-dependent transcription, and increasing levels of β-catenin either by transfection or using Wnt-3A was not sufficient to induce neurite outgrowth. Interestingly, Axin, which is also a substrate for GSK-3, was destabilized by Li+ and ectopic expression of Axin inhibited Li+-induced neurite outgrowth. Deletion analysis of Axin indicated that this inhibition required the GSK-3 binding site, but not the β-catenin binding site. Our results suggest that a signaling pathway involving Axin and GSK-3, but not β-catenin, regulates Li+-induced neurite outgrowth in Neuro-2a cells.
dc.format.extent673 - 686
dc.languageeng
dc.language.isoeng
dc.titleGlycogen synthase kinase-3 and Axin function in a β-catenin-independent pathway that regulates neurite outgrowth in neuroblastoma cells
dc.typeJournal Article
rioxxterms.versionofrecord10.1016/S1044-7431(03)00229-X
rioxxterms.licenseref.startdate2003
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfMolecular and Cellular Neuroscience
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR
pubs.volume24
pubs.embargo.termsNot known
dc.contributor.icrauthorVivanco, Mariaen


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