Department of Microbiology and Molecular Genetics, University of California, Irvine, CA, USA.
Differentiation. 2012 Sep;84(2):203-13. doi: 10.1016/j.diff.2012.06.004. Epub 2012 Jul 9.
Wnt ligands are secreted morphogens that control multiple developmental processes during embryogenesis and adult homeostasis. A diverse set of receptors and signals have been linked to individual Wnts, but the lack of tools for comparative analysis has limited the ability to determine which of these signals are general for the entire Wnt family, and which define subsets of differently acting ligands. We have created a versatile Gateway library of clones for all 19 human Wnts. An analysis comparing epitope-tagged and untagged versions of each ligand shows that despite their similar expression at the mRNA level, Wnts exhibit considerable variation in stability, processing and secretion. At least 14 out of the 19 Wnts activate β-catenin-dependent signaling, an activity that is cell type-dependent and tracks with the stabilization of β-catenin and LRP6 phosphorylation. We find that the core Wnt modification and secretion proteins Porcupine (PORCN) and Wntless (WLS) are essential for all Wnts to signal through β-catenin-dependent and independent pathways. This comprehensive toolkit provides critical tools and new insights into human Wnt gene expression and function.
Wnt 配体是分泌的形态发生素，可在胚胎发生和成人体内稳态期间控制多种发育过程。已经将多种受体和信号与单个 Wnt 相关联，但是缺乏用于比较分析的工具限制了确定这些信号中哪些是整个 Wnt 家族通用的，以及哪些信号定义了不同作用的配体的子集的能力。我们创建了一个用于所有 19 个人类 Wnt 的多功能 Gateway 克隆文库。对每个配体的表位标记和非标记版本进行的分析表明，尽管它们在 mRNA 水平上的表达相似，但 Wnt 在稳定性、加工和分泌方面存在很大差异。在 19 种 Wnt 中，至少有 14 种激活β-连环蛋白依赖性信号传导，这种活性是细胞类型依赖性的，并且与β-连环蛋白和 LRP6 磷酸化的稳定相关。我们发现核心 Wnt 修饰和分泌蛋白 Porcupine（PORCN）和 Wntless（WLS）对于所有 Wnt 信号转导通过β-连环蛋白依赖性和非依赖性途径都是必需的。这个全面的工具包为人类 Wnt 基因表达和功能提供了关键的工具和新的见解。
