Dkk-2, aa1-259, Recombinant, Human (Dickkopf-2, Dickkopf-related Protein 2 Precursor, Dkk-2, hDkk-2, UNQ682/PRO1316)

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 mediates Dkk-2 binding activities, and its interaction with B-propeller domains of LRP-5/6 has been mapped (2-4, 7). The 226aa, 35kD mature human Dkk-2 shares 96%, 97%, 97%, 97%, 97% and 98% aa identity with mouse, rat, canine, equine, bovine and porcine Dkk-2, respectively. Mouse Dkk-2 can activate the canonical Wnt signaling pathway in Xenopus embryos, showing evolutionary conservation of function (5). Dkk proteins modify Wnt engagement of a receptor complex composed of a Frizzled protein and a low-density lipoprotein receptor-related protein, either LRP-5 or LRP-6 (3). Also, Kremen-1 and Kremen-2 are high affinity receptors for Dkk-1 and Dkk-2 (9). When LRP-6 is overexpressed, direct high-affinity binding of Dkk-2 to LRP can enhance canonical Wnt signaling (6-8). However, when Dkk-2 and LRP-6 form a ternary complex with Kremen-2, 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, although it is expressed as early as periimplantation in mice (11). Mouse Dkk-1 or Dkk-2 deficiencies have opposite effects on bone homeostasis, despite down-regulating Wnt antagonism in both cases (12, 13). 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 (12). In contrast, Dkk-1 negatively regulates late osteoblast proliferation, which limits bone density (13). Dkk-2-deficient mice are blind, exhibiting faulty differentiation of corneal epithelium and ectopic blood vessels in the periocular mesenchyme (14, 15).\n\nSource: \nRecombinant corresponding to aa1-259 from human Dkk-2 expressed in CHO cells.\n\nMolecular Weight: \n~25.8kD\n\nEndotoxin Level:\n(same/less than)1EU/1ug (LAL)\n\nBiological Activity:\nMeasured in a competitive binding assay. When recombinant mouse Kremen-1 is immobilized at 4ug/ml (100ul/well), recombinant human Dkk-2 inhibits 50% binding of biotinylated recombinant human Dkk-1 (200ng/mL) at the concentration range of 1.5-6.0ug/ml.\n\nStorage and Stability:\nLyophilized powder may be stored at -20 degrees C. Stable for 12 months at -20 degrees C. Reconstitute with PBS. Aliquot to avoid repeated freezing and thawing. Store at -20 degrees C. Reconstituted product is stable for 6 months at -20 degrees C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.

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SPECIFICATIONS

Catalog Number

D3795-01C

Size

10ug

Form

Supplied as a lyophilized powder in PBS, EDTA, BSA. Reconstitute with PBS to 100ug/ml.

Purity

~95% (SDS-PAGE)

References

1. Monaghan, A.P. et al. (1999) Mech. Dev. 87:45. 2. Krupnik, V.E. et al. (1999) Gene 238:301. 3. Niehrs, C. (2006) Oncogene 25:7469. 4. Chen, L. et al. (2008) J. Biol. Chem. 283:23364. 5. Wu, W. et al. (2000) Current Biol. 10:1611. 6. Mao, B. et al. (2001) Nature 411:321. 7. Li, L. et al. (2002) J. Biol. Chem. 277:5977. 8. Brott, B. and S.Y. Sokol (2002) Mol. Cell. Biol. 22:6100. 9. Mao, B. et al. (2002) Nature 417:664. 10. Mao, B. and C. Niehrs (2003) Gene 302:179. 11. Zhang, Y. et al. (2009) J. Reprod. Dev. 55:17. 12. Li, X. et al. (2005) Nat. Genet. 37:945. 13. van der Horst, G. et al. (2005) J. Bone Miner. Res. 20:1867. 14. Mukhopadhyay, M. et al. (2006) Development 133:2149. 15. Gage, P.J. et al. (2008) Dev. Biol. 317:310.