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

R&D Systems, part of Bio-Techne | Catalog # 9836-DK

R&D Systems, part of Bio-Techne
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9836-DK-050
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Key Product Details

Source

CHO

Accession #

O94907

Conjugate

Unconjugated

Applications

Bioactivity

View all Dkk-1 Proteins and Enzymes »

Product Specifications

Source

Chinese Hamster Ovary cell line, CHO-derived human Dkk-1 protein
Asp142-His266, with a C-terminal 6-His tag

Purity

>95%, by SDS-PAGE visualized with Silver Staining and quantitative densitometry by Coomassie® Blue Staining.

Endotoxin Level

<0.10 EU per 1 μg of the protein by the LAL method.

N-terminal Sequence Analysis

Asp142

Predicted Molecular Mass

15 kDa

SDS-PAGE

17-33 kDa, reducing conditions

Activity

Measured by its binding ability in a functional ELISA.
When Recombinant Human LRP‑6 Fc Chimera (Catalog # 1505-LR) is immobilized onto a Goat anti-Human IgG Fc antibody coated plate, the concentration of Recombinant Human Dkk‑1 C-Terminal Fragment that produces 50% optimal binding response is 60-360 ng/mL.

Formulation, Preparation and Storage

9836-DK
Formulation Lyophilized from a 0.2 μm filtered solution in PBS.
Reconstitution
Reconstitute at 500 μg/mL in PBS.

Reconstitution Buffer Available:
Size / Price
Qty
Shipping The product is shipped with polar packs. Upon receipt, store it immediately at the temperature recommended below.
Stability & Storage
  • 12 months from date of receipt, ≤ -20 °C as supplied.
  • 1 month, 2 to 8 °C under sterile conditions after reconstitution.
  • 3 months, ≤ -20 °C under sterile conditions after reconstitution.

Background: Dkk-1

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).

References

  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. Brott, B.K. and S.Y. Sokol (2002) Mol. Cell. Biol. 22:6100.
  6. Chen, L. et al. (2013) Mol. Cancer 12:157.
  7. Chen, S. et al. (2011) Dev. Cell 21:848.
  8. Bourhis, E. et al. (2011) Structure 19:1433.
  9. Cheng, Z. et al. (2011) Nat. Struct. Mol. Biol. 18:1204.
  10. Mao, B. et al. (2002) Nature 417:664.
  11. Kemp, C. et al. (2005) Dev. Dyn. 233:1064.
  12. Adamska, M. et al. (2004) Dev. Biol. 272:134.
  13. Li, J. et al. (2006) Bone 39:754.
  14. Verani, R. et al. (2007) J. Neurochem. 100:242.
  15. Pinzone, J.J. et al. (2009) Blood 113:517.
  16. Morvan, F. et al. (2006) J. Bone Miner. Res. 21:934.
  17. Cappuccio, I. et al. (2005) J. Neurosci. 25:2647.
  18. Menezes, M.E. et al. (2012) Int. J. Cancer 130:1477.
  19. Li, S. et al. (2013) PLoS One 8:e84944.

Long Name

Dickkopf-1

Alternate Names

Dkk1

Entrez Gene IDs

22943 (Human); 13380 (Mouse); 102123735 (Cynomolgus Monkey)

Gene Symbol

DKK1

UniProt

O94907

Additional Dkk-1 Products

Product Documents for Recombinant Human Dkk-1 C-Terminal Fragment Protein, CF

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Product Specific Notices for Recombinant Human Dkk-1 C-Terminal Fragment Protein, CF

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