Dkk-2

The dickkopf (DKK) -related protein family is comprised of four central members, DKK-1 - 4, along with the distantly-related DKK family member DKK-11 (Soggy), which is thought to be a descendent of an ancestral DKK-3 precursor due to its unique sequence homology to DKK-3 and no other DKK family member. DKK family members, with the exception of the divergent Soggy, share two conserved cysteine-rich domains and show very little sequence similarity outside of these domains. Playing an important regulatory role in vertebrate development through localized inhibition of Wnt-regulated processes, including anterior-posterior axial patterning, limb development, somitogenesis, and eye formation, DKKs have also been implicated post-developmentally in bone formation, bone disease, cancer, and neurodegenerative diseases. DKK proteins typically play an important regulatory role in the Wnt/β-catenin signaling pathway by forming inhibitory complexes with LDL receptor-related proteins 5 and 6 (LRP5 and LRP6), which are essential components of the Wnt/β-catenin signaling system. LRP5 and LRP6 are single-pass transmembrane proteins that appear to act as co-receptors for Wnt ligands involved in the Wnt/β-catenin signaling cascade. DKK-2 has been shown to both inhibit and enhance canonical Wnt signaling; enhancing Wnt signaling through direct high-affinity binding of DKK-2 to LRP6 during LRP6 overexpression, while inhibiting Wnt signaling and promoting LRP6 internalization through the formation of a ternary complex between DKK-2, LRP6, and Kremen-2. Recombinant Human DKK-2 expressed in CHO cells is a glycoprotein that has a calculated molecular weight of 25.8 kDa and contains 234 amino acid residues. Due to glycosylation, human DKK-2 migrates at an apparent molecular weight of approximately 31-36 kDa by SDS-PAGE analysis under non-reducing conditions.