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Figure 2 | BMC Musculoskeletal Disorders

Figure 2

From: Elevated levels of β-catenin and fibronectin in three-dimensional collagen cultures of Dupuytren's disease cells are regulated by tension in vitro

Figure 2

Canonical Wnt/β-catenin pathway. β-catenin is a component of cell-cell adhesion structures (adherens junctions) [2022] and a key signaling factor in the Wnt pathway [10]. As shown here canonical Wnt signalling (Wnt/β-catenin) is defined by its inhibition of glycogen synthase kinase-3β (GSK-3β) catalyzed phosphorylation of β-catenin. Several factors, including Cer (cerebrus), WIF-1 (wnt-interacting protein), and sFRPs (secreted frizzled related proteins) and dickkopf-1 (Dkk) are known to antagonize Wnt signalling [6369]. However, upon Wnt stimulation several Fz-LRP downstream signalling components, including the phosphoprotein dishevelled (Dvl) [7072], GBP/Frat1 (GSK-3β Binding Protein) [73] and casein kinase I (CKIε) [74, 75], somehow co-operate to inhibit GSK-3β. This ultimately this leads to an increase in the cytosolic 'free' levels of β-catenin (uncomplexed to cadherin), and its accumulation within the nucleus where it binds to members of the Tcf/Lef (T-cell factor-lymphoid enhancer factor) transcription factor family to activate gene transcription in a cell-context dependent manner [2834]. In the absence of Wnt signalling, Axin/conductin [76, 77] in co-operation with the product of the tumour suppressor gene adenomatous polyposis coli (APC) [78, 79] facilitate GSK-3β mediated phosphorylation of β-catenin on N-terminal serine and threonine residues [80]. This hyper-phosphorylated form of β-catenin then binds to the F-box protein β TrCP, which targets β-catenin for degradation via the ubiquitin-proteosome pathway [8184].

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