A mode of regulation of β-catenin signaling activity in Xenopus embryos independent of its levels
A mode of regulation of β-catenin signaling activity in Xenopus embryos independent of its levels
复制标题
DOI：
10.1006/dbio.2000.9770
复制
发表时间：
2000-07-15
影响因子：
2.7
通讯作者：
Gumbiner, BM
中科院分区：
文献类型：
--
作者：
Guger, KA;Gumbiner, BM
β-连环蛋白的信号传导活性被认为是由一簇N-末端丝氨酸（GSK 3 β的推定位点）的磷酸化调节的。在文献中的流行模型中，这些位点的GSK 3 β依赖性磷酸化靶向β-连环蛋白以进行泛素介导的降解。Wnt信号传导抑制GSK 3 β活性，这阻断了降解，允许β-连环蛋白积累和信号传导。我们在这里表明，β-连环蛋白的活性不仅是由蛋白质的稳定性。β-连环蛋白假定的GSK 3 β磷酸化位点的突变增强了其信号传导活性，但这不能通过总蛋白或无钙粘蛋白蛋白的蛋白积累来解释。相反，在体内和体外信号传导测定中，突变蛋白具有比野生型高三倍的比活性。我们的结论是，N-末端丝氨酸传达一层的β-连环蛋白信号的调节除了这些网站施加在蛋白质的稳定性。(C)2000学术出版社
The signaling activity of beta-catenin is thought to be regulated by phosphorylation of a cluster of N-terminal serines, putative sites for GSK3 beta. In the prevailing model in the literature, GSK3 beta-dependent phosphorylation of these sites targets beta-catenin for ubiquitin-mediated degradation. Wnt signaling inhibits GSK3 beta activity and this blocks degradation, allowing beta-catenin to accumulate and signal. We show here that beta-catenin activity is not regulated solely by protein stability. Mutations in the putative GSK3 beta phosphorylation sites of beta-catenin enhance its signaling activity, but this cannot be accounted for by accumulation of either total or cadherin-free protein. Instead, the mutant protein has a threefold higher specific activity than the wild type both in vivo and in an in vitro signaling assay. We conclude that the N-terminal serines convey a layer of regulation upon beta-catenin signaling in addition to the effects these sites exert upon protein stability. (C) 2000 Academic Press