Mouse Dkk-2 Antibody

Dickkopf related protein 2 (Dkk-2) is a member of the Dickkopf family of secreted Wnt modulators (1-3). Dkk proteins contain a signal peptide and two conserved cysteine-rich domains that are separated by a linker region. The second cysteine-rich domain, which shows a configuration of cysteines conserved in prokineticin and colipase families, mediates Dkk-2 binding activities (2-4). The 226 amino acid (aa), ~35 kDa mature mouse Dkk-2 shares 41% and 34% aa identity with mouse Dkk-1 and Dkk-4, respectively. It also shares 99%, 96%, 96%, 96% and 94% aa identity with rat, human, canine, equine and bovine Dkk-2, respectively, and can activate the canonical Wnt signaling pathway in Xenopus embryos (5). Dkk proteins modify Wnt engagement of a receptor complex composed of a Frizzled protein and a low-density lipoprotein receptor-related protein, either LRP5 or LRP6 (3). When LRP6 is overexpressed, direct high-affinity binding of Dkk-2 to LRP can enhance canonical Wnt signaling (6-8). However, when Dkk-2 and LRP6 form a ternary complex with Kremen2, Wnt signaling is inhibited due to internalization of Dkk-2/LRP6/Krm2 complexes (9, 10). Thus, depending on the cellular context, Dkk-2 can either activate or inhibit canonical Wnt signaling (3). In contrast, binding of Dkk-1 or Dkk-4 to LRP is consistently antagonistic (3). Dkk proteins are expressed in mesenchymal tissues and control epithelial transformations. Dkk-2 expression has been studied most in bone and eye. Mouse Dkk-1 or Dkk-2 deficiencies have opposite effects on bone homeostasis, despite downregulating Wnt antagonism in both cases (11, 12). Dkk-2 expression is induced by Wnts in bone, and is thought to enhance bone density by promoting terminal differentiation of osteoblasts and mineral deposition (11). In contrast, Dkk-1 negatively regulates late osteoblast proliferation, which limits bone density (12). Dkk-2-deficient mice are blind due to faulty differentiation of corneal epithelium (13).