Wnt proteins comprise a major family of signaling molecules that orchestrate and influence a myriad of cell
biological and developmental processes. Although our understanding of the role of Wnt signaling in regulating development and affecting disease, such as
cancer, has been ever increasing, the study of the
Wnt proteins themselves has been painstaking and slow moving. Despite advances in the biochemical characterization of
Wnt proteins, many mysteries remain unsolved. In contrast to other developmental signaling molecules, such as
fibroblast growth factors (FGF),
transforming growth factors (TGFβ), and Sonic hedgehog (Shh),
Wnt proteins have not conformed to many standard methods of
protein production, such as bacterial overexpression, and analysis, such as
ligand-receptor binding assays. The reasons for their recalcitrant nature are likely a consequence of the complex set of posttranslational modifications involving several highly specialized and poorly characterized processing
enzymes. With the recent description of the first
Wnt protein structure, the time is ripe to uncover and possibly resolve many of the remaining issues surrounding
Wnt proteins and their interactions. Here we describe the process of maturation of Wnt from its initial translation to its eventual release from a cell and interactions in the extracellular environment.