Recombinant Human/Mouse Frizzled-2 Fc Chimera Protein, CF

Wnt signaling is involved in variety of developmental processes including cell fate determination, cell polarity, tissue patterning and control of cell proliferation. Members of the Frizzled family of proteins serve as receptors for the Wnt signaling pathway. The founding member of this family was identified in Drosophila based on its role in tissue polarity in the adult cuticle and named for the disorganized appearance of bristle hairs on the mutant. Ten mammalian Frizzled genes have been identified to date. The predicted structure of Frizzled proteins is similar among all family members, containing a divergent N-terminal signal peptide, a highly conserved extracellular cysteine-rich domain, a variable-length linker region, a seven-pass transmembrane domain, and a variable-length C-terminal tail. One of the most conserved regions of the Frizzled proteins is the extracellular cysteine-rich domain (CRD) which spans approximately 120 amino acids (aa) and contains 10 invariant cysteines (1). Human and mouse Frizzled-2 are 100% identical at the aa level. Frizzled-2 expression is greater in embryonic than adult tissues, with heart, brain, lung, kidney and gut showing the highest levels (2). In addition, Frizzled-2 is expressed during migration and proliferation of neural crest cells that populate the heart and great arteries (3). However, Frizzled-2 may not be strictly involved in developmental processes, as its expression is also up-regulated in myofibroblasts during tissue repair after myocardial infarction (4). Frizzled-2 is implicated in the Wnt/Ca2+ pathway, a mechanism by which Wnt-5a signaling results in calcium release from intracellular stores and activation of PKC and calmodulin-dependent protein kinase (5). Secreted frizzled related proteins (sFRPs), antagonists of the Wnt pathway, have been shown to interact with both Wnt ligands and Frizzled receptors (6).