Tolwinski Nicholas S, Wieschaus Eric
Howard Hughes Medical Institute, Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Trends Genet. 2004 Apr;20(4):177-81. doi: 10.1016/j.tig.2004.02.003.
Recent research on the WNT signaling pathway warrants a reassessment of the basic mechanism that transmits signal from the membrane-bound receptor to the nucleus. This article incorporates these findings into a revised model for pathway activation. We propose that the control of Axin stability, rather than the control of ZW3 phosphorylation of the Armadillo protein, is the key step in signaling. Axin degradation is controlled by a stabilizing effect of ZW3-dependent phosphorylation, and a destabilizing effect of active Arrow. Removing Axin enables Armadillo to accumulate and re-localize to the nucleus. We argue that nuclear localization of Armadillo is required for transcriptional pathway activity. Finally, we speculate on the effects this revision will have on the major questions facing the WNT field of research.
近期对WNT信号通路的研究有必要重新评估将信号从膜结合受体传递至细胞核的基本机制。本文将这些研究结果纳入了一个经修订的通路激活模型。我们提出，对Axin稳定性的控制，而非对犰狳蛋白的ZW3磷酸化的控制，是信号传导中的关键步骤。Axin的降解受ZW3依赖性磷酸化的稳定作用以及活性箭蛋白的去稳定作用的控制。去除Axin可使犰狳蛋白积累并重新定位于细胞核。我们认为犰狳蛋白的核定位是转录通路活性所必需的。最后，我们推测了这一修订对WNT研究领域所面临的主要问题将产生的影响。
