Wnt Ligands (Wnts)

Wnt ligands are a large family of secreted glycoproteins that are cysteine-rich and highly hydrophobic. Wnts are produced as precursor proteins that contain a short N-terminal signal sequence and a mature segment that varies in length from approximately 320 to 400 amino acids. In vertebrates, there are 19 different Wnt proteins whose expression is spatially and temporally regulated during development. Wnts activate intracellular signaling pathways by binding to one of several Frizzled family receptors and in some cases, a co-receptor, such as Lipoprotein Receptor-related Protein (LRP)-5, LRP-6, Related to tyrosine kinase (Ryk), or Receptor tyrosine kinase-like Orphan Receptor (ROR). In general, there are three primary Wnt signaling pathways. The first is commonly called the canonical beta-Catenin-dependent pathway and ultimately culminates in beta-Catenin accumulation and TCF/LEF-1-mediated gene transcription. The other two less well-defined pathways include the Wnt/Ca²⁺ pathway and the planar cell polarity (PCP) pathway. Collectively, these pathways regulate cell survival, cell proliferation, cell fate determination, cell polarity, tissue patterning, and tissue homeostasis.