Recombinant Human Dkk-1 C-Terminal Fragment Protein, CF

This product is produced by and ships from R&D Systems, Inc., a Bio-Techne brand.

Dickkopf related protein 1 (Dkk-1) is the founding member of the Dickkopf family of proteins that includes Dkk-1, -2, -3, -4, and a related protein, Soggy (1, 2). Dkk proteins are secreted proteins that contain two conserved cysteine-rich domains (CRDs), CRD1 (N-terminal) and CRD2 (C-terminal), separated by a linker region. Each domain contains ten cysteine residues (1-3). Mature human Dkk-1 is a 40 kDa glycosylated protein. Within the C-terminal fragment [amino acids (aa) 142-266] that includes the CRD2, human DKK-1 shares 96% amino acid sequence identity with mouse Dkk-1. Dkk-1 antagonizes Wnt/beta-catenin signaling, an activity for which the C-terminal CRD2 is both necessary and sufficient (4, 5), and the C-terminal fragment has been shown to interact with LRP5 or LRP6 (6). However, crystallographic studies have shown that Dkk-1 interacts with LRP-6 as a bipartite inhibitor, with both CRDs binding the extracellular domain of LRP-6 simultaneously (7-9).  Dkk-1/LRP-6/Krm2 complex internalization has been shown to down-regulate Wnt signaling (4, 10). Dkk-1 is expressed throughout development and antagonizes Wnt-7a during limb development (11, 12). Other sites of expression include developing neurons, hair follicles, and the retina (13, 14). The balance between Wnt signaling and Dkk-1 inhibition is critical for bone formation and homeostasis (15). Insufficient or excess Dkk-1 activity in bone results in increased or decreased bone density, respectively (13, 16). In adults, Dkk-1 is expressed in osteoblasts and osteocytes, and neurons. Cerebral ischemia induces Dkk-1 expression, which contributes to neuronal cell death (17). Dkk-1 also likely has a complex role in cancer, as it has been shown to act as a tumor suppressor and also to promote metastasis (6, 18-19).

Array 9836-DK

• Dkk-1 Antibodies
• Dkk-1 Antibody Pair
• Dkk-1 ELISA Kit
• Dkk-1 Lysate
• Dkk-1 Proteins and Enzymes
• Dkk-1 ELISAs