A role of dishevelled in relocating axin to the plasma membrane during wingless signaling
A role of dishevelled in relocating axin to the plasma membrane during wingless signaling
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DOI：
10.1016/s0960-9822(03)00370-1
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发表时间：
2003-05-27
期刊：
影响因子：
9.2
通讯作者：
Bienz, M
中科院分区：
文献类型：
--
作者：
Cliffe, A;Hamada, F;Bienz, M
令状信号传导导致基因转录发生变化，这对于正常和恶性发育至关重要 [1, 2]。典型令状通路的关键效应器是β-连环蛋白，或果蝇犰狳。在缺乏 Writ 配体的情况下，β-连环蛋白被 Axin 复合物磷酸化，这使其被泛素系统快速降解。轴蛋白在该复合物中充当支架，组装 β-连环蛋白底物和激酶（酪蛋白激酶 I [CKI] 和糖原合酶激酶 3P [GSK3]）[3, 4]。腺瘤性结肠息肉病 (APC) 肿瘤抑制因子也与 Axin 复合物结合，从而促进 β-连环蛋白的降解 [5, 6]。在令状信号传导中，该复合物被抑制；因此，β-连环蛋白积累并与 TCF 蛋白结合，刺激 Writ 靶基因的转录 [1, 2]。 Wnt 诱导的 Axin 复合物抑制依赖于 Disheveled (Dsh) [7-9]，这是一种可以与 Axin 结合的细胞质蛋白 [10, 11]，但这种抑制的机制尚不清楚。在这里，我们发现 Wingless 信号传导导致果蝇轴蛋白从细胞质显着转移到质膜。此重定位取决于 Dsh。它可能允许随后通过 Wingless 信号传导使 Axin 复合物失活。
Writ signaling causes changes in gene transcription that are pivotal for normal and malignant development [1, 2]. A key effector of the canonical Writ pathway is beta-catenin, or Drosophila Armadillo. In the absence of Writ ligand, beta-catenin is phosphorylated by the Axin complex, which earmarks it for rapid degradation by the ubiquitin system. Axin acts as a scaffold in this complex, to assemble beta-catenin substrate and kinases (casein kinase I [CKI] and glycogen synthase kinase 3P [GSK3]) [3, 4]. The Adenomatous polyposis coli (APC) tumor suppressor also binds to the Axin complex, thereby promoting the degradation of beta-catenin [5, 6]. In Writ signaling, this complex is inhibited; as a consequence, beta-catenin accumulates and binds to TCF proteins to stimulate the transcription of Writ target genes [1, 2]. Wnt-induced inhibition of the Axin complex depends on Dishevelled (Dsh) [7-9], a cytoplasmic protein that can bind to Axin [10, 11], but the mechanism of this inhibition is not understood. Here, we show that Wingless signaling causes a striking relocation of Drosophila Axin from the cytoplasm to the plasma membrane. This relocation depends on Dsh. It may permit the subsequent inactivation of the Axin complex by Wingless signaling.