破坏复合物的解聚和AXIN向膜上的招募
中文名称
通路描述
在WNT配体刺激下，AXIN和GSK3beta通过与DVL相互作用招募到质膜上。膜结合DVL和GSK3beta的聚合以及CSNK1介导的LRP5/6磷酸化建立了增强WNT信号下AXIN膜招募的级联机制。在 Xenopus 卵母细胞中，但并非所有系统中，AXIN以限制浓度存在，被认为是破坏复合物组装的限速步骤。WNT刺激下AXIN从破坏复合物中的招募有效破坏了破坏复合物，并促进了游离β-catenin的积累。AXIN与破坏复合物的结合也受磷酸化调节。在活性破坏复合物中，AXIN由GSK3beta磷酸化；蛋白磷酸酶1（PP1）或蛋白磷酸酶2A（PP2A）的去磷酸化破坏AXIN与其他破坏复合物组分相互作用，并促进其解聚。游离AXIN还受依赖TANKYRASE 1和2的多腺苷二磷酸核糖基转移酶降解。
英文描述
Disassembly of the destruction complex and recruitment of AXIN to the membrane Upon stimulation with WNT ligand, AXIN and GSK3beta are recruited to the plasma membrane through interaction with DVL (Tamai et al, 2004; Mao et al, 2001; reviewed in He et al, 2004). Polymerization of membrane-associated DVL and GSK3beta- and CSNK1-mediated phosphorylation of LRP5/6 establish a feed-forward mechanism for enhanced membrane recruitment of AXIN upon WNT signaling (Tamai et al, 2004; Cong et al, 2004; Zeng et al, 2005; Bilic et al, 2007). In Xenopus oocytes, but not necessarily all sytems, AXIN is present in limiting concentrations and is considered rate limiting for the assembly of the destruction complex (Lee et al, 2003; Benchabane et al, 2008; Tan et al, 2012; reviewed in MacDonald et al, 2009). The recruitment of AXIN away from the destruction complex upon WNT stimulation effectively destabilizes the destruction complex and contributes to the accumulation of free beta-catenin (Kikuchi, 1999; Lee et al, 2003). AXIN association with the destruction complex is also regulated by phosphorylation. In the active destruction complex, AXIN is phosphorylated by GSK3beta; dephosphorylation by protein phosphatase 1 (PP1) or protein phosphatase 2A (PP2A) destabilizes the interaction of AXIN with the other components of the destruction complex and promotes its disassembly (Luo et al, 2007; Willert et al, 1999; Jho et al, 1999). Free AXIN is also subject to degradation by the 26S proteasome in a manner that depends on the poly-ADP-ribosylating enzymes tankyrase 1 and 2 (Huang et al, 2009).
所含基因
24 个基因