Bcakground 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 separated by a linker region. Each domain contains ten cysteine residues (1-3). Mature human Dkk-1 is a 40 kDa glycosylated protein that shares 86%, 87%, 90% and 91% aa sequence identity with mouse, rat, rabbit and bovine Dkk-1, respectively. It also shares 42% and 36% aa identity with human Dkk-2 and Dkk-4, respectively. Dkk-1 and Dkk-4 are well documented antagonists of the canonical Wnt signaling pathway (1, 2). This pathway is activated by Wnt engagement of a receptor complex composed of the Frizzled proteins and one of two low-density lipoprotein receptor-related proteins, LRP5 or LRP6 (4). Dkk-1 antagonizes Wnt by forming ternary complexes of LRP5/6 with Kremen1 or Kremen2 (4, 5). Dkk-1/LRP6/Krm2 complex internalization has been shown to down-regulate Wnt signaling (4, 5). Dkk-1 is expressed throughout development and antagonizes Wnt-7a during limb development (6, 7). Other sites of expression include developing neurons, hair follicles and the retina of the eye (8, 9). The balance between Wnt signaling and Dkk-1 inhibition is critical for bone formation and homeostasis (10). Insufficient or excess Dkk-1 activity in bone results in increased or decreased bone density, respectively (8, 11). In adults, Dkk-1 is expressed in osteoblasts and osteocytes, and neurons. Cerebral ischemia induces Dkk-1 expression, which contributes to neuronal cell death (12). Reference 1. Krupnik, V.E. et al. (1999) Gene 238:301. 2. Niehrs, C. (2006) Oncogene 25:7469. 3. Bullock, C.M. et al. (2004) Mol. Pharmacol. 65:582. 4. Mao, B. et al. (2001) Nature 411:321. 5. Mao, B. et al. (2002) Nature 417:664. 6. Kemp, C. et al. (2005) Dev. Dyn. 233:1064. 7. Adamska, M. et al. (2004) Dev. Biol. 272:134. 8. Li, J. et al. (2006) Bone 36:754. 9. Verani, R. et al. (2006) J. Neurochem. 101:242. 10. Pinzone, J.J. et al. (2009) Blood 113:517. 11. Morvan, F. et al. (2006) J. Bone Miner. Res. 21:934. 12. Cappuccio, I. et al. (2005) J. Neurosci. 25:2647. Specifications Synonyms Dickkopf-1; dickkopf-related protein 1; Dkk1; Dkk-1; hDkk-1; SKdickkopf-1 like Accession # O94907 Source Human embryonic kidney cell, HEK293-derived human Dkk1 protein Met 2-His 266 Predicted Moleucular weight 26.6 kDa Components and Storage Formulation Solution protein Dissolved in sterile PBS buffer . This solution can be diluted into other aqueous buffers. Centrifuge the vial prior to opening. Storage and Stability Avoid repeated freeze-thaw cycles. It is recommended that the protein be aliquoted for optimal storage. 12 months from date of receipt, -20 to -70 °C as supplied. Shipping Shipping with dry ice Quality Purity > 95%, determined by SDS-PAGE. Endotoxin Stability
