The canonical Wingless signalling pathway consists of two main branches. One of these is active when Wingless (WG) ligand is bound to Frizzled (FZ/FZ2) receptors and the other is active when there is no binding. The default pathway is with no WG ligand bound to the FZ/FZ2 receptor. Armadillo (ARM) is sequestered to the 'destruction complex', is phosphorylated and ubiquitinated, and then degraded by the proteasome. The ARM concentration in the cytoplasm is depleted so there is no complex formed with Pangolin (PAN) in the nucleus and gene transcription is inactivated. However, when WG binds with FZ/FZ2, a plasma membrane receptor complex with Arrow (ARR) is formed. ARR is in turn phosphorylated by the membrane-anchored kinase Gish (GISH) and membrane localised Shaggy (SGG). The molecules Dishevelled (DSH) and Axin (AXN) are recruited to ARR and FZ/FZ2 respectively, the former along with its interaction partners in the 'destruction complex'. The binding of DSH to AXN, deactivates SGG and leads to the degradation of AXN. This, along with dephosphorylation of the 'destruction complex' leads to the release of ARM and the disassembly of the 'destruction complex'. The levels of cytoplasmic AXN drop and ARM increase with the result that sufficient ARM transports from the cytoplasm to the nucleus to form a complex with PAN which leads to transcriptional activation.
Kruger, R, Salic, A, Kirschner, MW, Lee, E, Heinrich, R
Ilyas, M
Kikuchi, A, Yamamoto, H, Kishida, S
Stadeli, R, Hoffmans, R, Basler, K
Logan, CY, Nusse, R
Tolwinski, NS, Wieschaus, E
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