Structure-function relationships and evolution of wnt signaling molecules

WNT配体包括一个分泌的、疏水的糖蛋白大家族，它们控制着所有后生动物的各种发育和成体过程。虽然Wnt信号转导过程在细胞水平上得到了越来越多的了解，但我们对Wnt配体、受体和拮抗剂的分子结构的了解非常有限。关于Wnt信号分子的结构-功能关系的信息被认为是详细了解配体/受体相互作用以及设计新型激动剂或拮抗剂配体的关键。线虫因其简单的体型、易操控和进化影响，已被证明是研究Wnt信号的有吸引力的模式生物。此外，还分离到了一套完整的Wnt信号分子。因此，在我们的结构-功能分析中，我们选择了规范和非规范的Wnt蛋白以及来自九头蛇和脊椎动物(小鼠)的Dickkopf(DKK)分子，以努力追溯这些蛋白的分子进化。

Wnt ligands comprise a large family of secreted, hydrophobic glycoproteins that control a variety of developmental and adult processes in all metazoan organisms. Although Wnt signaling processes are increasingly understood at the cellular level, our knowledge of the molecular structures of Wnt ligands, receptors and antagonists is very limited. Information about structure-function relationships in Wnt signaling molecules is supposed to be critical for a detailed understanding of ligand/receptor interactions and for the design of novel agonistic or antagonistic ligands. Cnidarians have proven attractive model organisms for the research on Wnt signaling due to their simple body plan, easy manipulation and evolutionary impact. In addition, a complete set of Wnt signaling molecules has been isolated from a cnidarian species. For our structure-function analysis we have therefore chosen both, canonical and non-canonical Wnt proteins as well as dickkopf (dkk) molecules from Hydra and vertebrates (mouse) in an effort to retrace the molecular evolution of these proteins.