The axis-inducing activity, stability, and subcellular distribution of beta-catenin is regulated in Xenopus embryos by glycogen synthase kinase 3
The axis-inducing activity, stability, and subcellular distribution of beta-catenin is regulated in Xenopus embryos by glycogen synthase kinase 3
复制标题
DOI：
10.1101/gad.10.12.1443
复制
发表时间：
1996-06-15
影响因子：
10.5
通讯作者：
Moon, RT
中科院分区：
文献类型：
--
作者：
Yost, C;Torres, M;Moon, RT
丝氨酸/苏氨酸激酶Xgsk-3和细胞内蛋白β -catenin是爪蟾建立背-腹轴所必需的。尽管来自果蝇的遗传证据表明Xgsk-3是β -连环蛋白的上游，但这些蛋白之间的直接相互作用尚未得到证实。我们证明体内β -连环蛋白的磷酸化需要体外氨基末端Xgsk-3磷酸化位点，这在果蝇蛋白犰狳中是保守的。缺乏该位点的β -catenin突变体在爪蟾胚胎中诱导异位轴更活跃，并且在Xgsk-3活性存在时比野生型β -catenin更稳定，支持Xgsk-3是β -catenin通过氨基末端作用的负调节因子的假设。用显性阴性突变体抑制内源性Xgsk-3功能导致异位β -连环蛋白稳态水平增加，表明Xgsk-3功能破坏β -连环蛋白的稳定，从而减少可用于信号传导的β -连环蛋白的数量。在显性阴性的Xgsk-3突变体存在时，细胞核内内源性β -连环蛋白水平增加，这表明Xgsk-3的作用是调节特定亚细胞区室内β -连环蛋白的稳态水平。这些研究为了解Xgsk-3与β -catenin在爪蟾早期胚胎背-腹轴形成过程中的相互作用提供了基础。
The serine/threonine kinase Xgsk-3 and the intracellular protein beta-catenin are necessary for the establishment of the dorsal-ventral axis in Xenopus. Although genetic evidence from Drosophila indicates that Xgsk-3 is upstream of beta-catenin, direct interactions between these proteins have not been demonstrated. We demonstrate that phosphorylation of beta-catenin in vivo requires an in vitro amino-terminal Xgsk-3 phosphorylation site, which is conserved in the Drosophila protein armadillo. beta-Catenin mutants lacking this site are more active in inducing an ectopic axis in Xenopus embryos and are more stable than wild-type beta-catenin in the presence of Xgsk-3 activity, supporting the hypothesis that Xgsk-3 is a negative regulator of beta-catenin that acts through the amino-terminal site. Inhibition of endogenous Xgsk-3 function with a dominant-negative mutant leads to an increase in the steady-state levels of ectopic beta-catenin, indicating that Xgsk-3 functions to destabilize beta-catenin and thus decrease the amount of beta-catenin available for signaling. The levels of endogenous beta-catenin in the nucleus increases in the presence of the dominant-negative Xgsk-3 mutant, suggesting that a role of Xgsk-3 is to regulate the steady-state levels of beta-catenin within specific subcellular compartments. These studies provide a basis for understanding the interaction between Xgsk-3 and beta-catenin in the establishment of the dorsal-ventral axis in early Xenopus embryos.