Wingless pathway

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.

经典的无翅信号通路主要由两个主要分支构成。当无翅（WG）配体与佛洛斯林（FZ/FZ2）受体结合时，其中一个分支被激活；而另一个分支则在无结合时处于活跃状态。默认情况下，FZ/FZ2受体未与WG配体结合。装甲蛋白（ARM）被隔离至‘降解复合体’中，随后被磷酸化和泛素化，最终由蛋白酶体降解。细胞质中ARM的浓度降低，因此无法与穿山甲蛋白（PAN）在细胞核中形成复合体，从而导致基因转录失活。然而，当WG与FZ/FZ2结合时，会形成包含箭头蛋白（ARR）的质膜受体复合物。ARR随后被膜锚定激酶吉什（GISH）和膜定位的毛茸茸蛋白（SGG）磷酸化。无序蛋白（DSH）和阿克辛蛋白（AXN）分别被招募至ARR和FZ/FZ2，前者与其在‘降解复合体’中的相互作用伙伴一同。DSH与AXN的结合会失活SGG，并导致AXN的降解。这，加上‘降解复合体’的脱磷酸化，导致ARM的释放和‘降解复合体’的解聚。细胞质中AXN的水平下降，ARM水平上升，从而使得足够的ARM从细胞质转运至细胞核，与PAN形成复合物，进而导致转录激活。