Communication -: Axin, a negative regulator of the Wnt signaling pathway, directly interacts with adenomatous polyposis coli and regulates the stabilization of β-catenin
Communication -: Axin, a negative regulator of the Wnt signaling pathway, directly interacts with adenomatous polyposis coli and regulates the stabilization of β-catenin
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DOI：
10.1074/jbc.273.18.10823
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发表时间：
1998-05-01
影响因子：
4.8
通讯作者：
Kikuchi, A
中科院分区：
文献类型：
--
作者：
Kishida, S;Yamamoto, H;Kikuchi, A
Axin的G蛋白信号传导（RGS）结构域调节因子是Wnt信号传导途径的负调节因子，在COS、293和L细胞中与全长腺瘤性息肉病（APC）形成复合物，但在SW 480和DLD-1细胞中不与截短的APC形成复合物。RGS结构域直接与含有APC的20个氨基酸重复序列的区域相互作用，但不与含有APC的15个氨基酸重复序列的区域相互作用，尽管已知这两个区域都与β-连环蛋白结合。在含有7个20-氨基酸重复序列的区域中，含有后5个重复序列的区域与Axin的RGS结构域结合。Axin和beta-catenin同时与APC相互作用。此外，Axin刺激COS细胞中β-连环蛋白的降解。结合我们最近的观察，即Axin直接与糖原合成酶激酶-3 β（GSK-3 β）和β-连环蛋白相互作用，并且它促进β-连环蛋白的GSK-3 β依赖性磷酸化，这些结果表明Axin、APC、GSK-3 β和β-连环蛋白形成四聚体复合物，导致β-连环蛋白稳定性的调节。
The regulators of G protein signaling (RGS) domain of Axin, a negative regulator of the Wnt signaling pathway, made a complex with full-length adenomatous polyposis coli (APC) in COS, 293, and L cells but not with truncated APC in SW480 or DLD-1 cells. The RGS domain directly interacted with the region containing the 20-amino acid repeats but not with that containing the 15-amino acid repeats of APC, although both regions are known to bind to beta-catenin. In the region containing seven 20-amino acid repeats, the region containing the latter five repeats bound to the RGS domain of Axin. Axin and beta-catenin simultaneously interacted with APC. Furthermore, Axin stimulated the degradation of beta-catenin in COS cells. Taken together with our recent observations that Axin directly interacts with glycogen synthase kinase-3 beta (GSK-3 beta) and beta-catenin and that it promotes GSK-3 beta-dependent phosphorylation of beta-catenin, these results suggest that Axin, APC, GSK-3 beta, and beta-catenin make a tetrameric complex, resulting in the regulation of the stabilization of beta-catenin.