R-spondin proteins -: A novel link to β-catenin activation
R-spondin proteins -: A novel link to β-catenin activation
复制标题
DOI：
10.4161/cc.5.1.2305
复制
发表时间：
2006-01-01
期刊：
影响因子：
4.3
通讯作者：
Funk, WD
中科院分区：
文献类型：
--
作者：
Kim, KA;Zhao, JS;Funk, WD
R-spondin（Rspo）蛋白家族是最近描述的一组四种不同的人类分泌蛋白。报道的Rspo蛋白的活性包括在脊椎动物发育中的重要作用，并且它们的配体类型活性与经典Wnt配体的活性基本上重叠，因为Rspo和经典Wnt信号传导都导致β-连环蛋白的活化。在一个通用的功能筛选人类分泌的蛋白质，使用转基因小鼠模型，我们确定了人R-spondin 1（hRspo 1）蛋白作为一个有效的和特定的有丝分裂原的胃肠道上皮细胞，并证明了一个潜在的治疗应用的蛋白质在小鼠模型中的癌症治疗诱导的粘膜炎。与以前的研究相反，我们的数据表明Wnt和Rspo配体活性之间只有部分重叠，这表明Rspo蛋白可能存在独立的受体/信号通路，这些受体/信号通路在β-连环蛋白水平上与Wnt交叉。在这里，我们总结了目前报道的数据Rspo家庭和讨论这些结果的替代作用机制。我们已经通过显示所有四个人Rspo家族成员都能够诱导上皮细胞增殖并报告了第一个非脊椎动物Rspo家族成员来扩展我们对Rspo蛋白的潜在治疗应用的观察。
The R-spondin (Rspo) protein family is a recently described group of four distinct human secreted proteins. Reported activities for Rspo proteins include essential roles in vertebrate development and their ligand-type activities overlap substantially with those of the canonical Wnt ligands in that both Rspo and canonical Wnt signaling result in the activation of beta-catenin. In a general functional screen for human secreted proteins using transgenic mouse models, we identified human R-spondin1 (hRspo1) protein as a potent and specific mitogen for the gastrointestinal epithelium and demonstrated a potential therapeutic application for the protein in mouse models of cancer therapy-induced mucositis. In contrast to previous studies, our data indicated only partial overlap between Wnt and Rspo ligand activities, suggesting that there may be independent receptor/signaling pathways for Rspo proteins that intersect those of Wnt at the level of beta-catenin. Here we summarize the current reported data on the Rspo family and discuss these results in terms of alternate mechanisms of action. We have extended our observations on the potential therapeutic application of Rspo proteins by showing that all four human Rspo family members are capable of inducing epithelial proliferation and report the first non-vertebrate Rspo family member.