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Recombinant human DKK-1 protein

QK068

Brand: Qkine

Dickkopf-related protein 1 (DKK-1) is a key player in the Wnt signaling pathway and regulates embryonic development, tissue balance, and diseases, including cancer. DKK-1 is a member of the DKK protein family and acts as a potent Wnt pathway antagonist.

In cell culture, DKK-1 is pivotal for controlling cell fate, self-renewal, and differentiation by inhibiting the canonical Wnt/β-catenin pathway through LRP5/6 co-receptors. DKK-1 has been widely used in various applications including guiding stem cell differentiation, particularly in neural and osteogenic pathways, and mimicking dysregulated Wnt signaling seen in cancers. Its inhibitory role is also crucial for anterior development.

Human DKK-1 has a molecular weight of 25.7 kDa, animal origin-free, carrier-free and tag-free to ensure its purity with exceptional lot-to-lot consistency. DKK-1 is suitable for the culture of reproducible and high-quality stem cells and other relevant cells.

Currency: 

Product name Catalog number Pack size Price Price (USD) Price (GBP) Price (EUR)
Recombinant human DKK-1 protein, 25 µg QK068-0025 25 µg (select above) $ 355.00 £ 255.00 € 298.00
Recombinant human DKK-1 protein, 50 µg QK068-0050 50 µg (select above) $ 515.00 £ 380.00 € 444.00
Recombinant human DKK-1 protein, 100 µg QK068-0100 100 µg (select above) $ 760.00 £ 560.00 € 655.00
Recombinant human DKK-1 protein, 500 µg QK068-0500 500 µg (select above) $ 3,100.00 £ 2,300.00 € 2,687.00
Recombinant human DKK-1 protein, 1000 µg QK068-1000 1000 µg (select above) $ 4,950.00 £ 3,600.00 € 4,205.00

Note: prices shown do not include shipping and handling charges.

Qkine company name and logo are the property of Qkine Ltd. UK.

Alternative protein names
Dickkopf-related protein 1, Dickkopf-1, DKK1, hDkk-1, SK, Dickkopf-like protein 1, Dickkopf 1 homolog, Dickkopf WNT signaling pathway inhibitor
Species reactivity

human

species similarity:
mouse – 86%
rat – 86%
porcine – 33%
bovine – 93%

Frequently used together with:

Summary

  • High purity human DKK-1 protein (Uniprot number: O94907)
  • >98%, by SDS-PAGE quantitative densitometry
  • Source: Expressed in E. coli
  • 25.7 kDa, monomer
  • Animal origin-free (AOF) and carrier protein-free
  • Manufactured in Cambridge, UK
  • Lyophilized from acetonitrile/TFA/mannitol
  • Resuspend in water at >100 µg/ml, prepare single-use aliquots, add carrier protein if desired and store frozen at -20°C or -80°C
Handling and Storage FAQ

Featured applications

  • Drug discovery in endocrinology
  • Drug discovery in inflammation
  • Drug discovery in metabolism
  • Development of metabolic therapeutics
  • Cell growth, differentiation, and inflammation 

Bioactivity

Bioactivity graph showing the EC50 of 12 ng/mL (0.47 nM) for Qkine recombinant DKK1

DKK-1 activity is determined using the Wnt-3a-responsive firefly luciferase reporter assay. Transfected HEK293T cells are treated in triplicate with a serial dilution of DKK-1 and a standard concentration of Wnt-3a for 24 hours. Firefly luciferase activity is measured and normalised to the control Renilla luciferase activity. EC50 = 12 ng/mL (0.47 nM). Data from Qk068 lot #204593.

Purity

SDS-PAGE gel showing the high purity reduced and non-reduced forms of DKK1

Recombinant DKK-1 migrates as a single band at approximately 26 kDa in non-reduced (NR) and at approximately 30 kDa in reduced conditions. No contaminating protein bands are present. The purified recombinant protein (3 µg) was resolved using 15% w/v SDS-PAGE in reduced (+β-mercaptothanol, R) and non-reduced (NR) conditions and stained with Coomassie Brilliant Blue R250. Data from Qk068 lot #204593.

Further quality assays

  • Mass spectrometry, single species with the expected mass
  • Endotoxin: <0.005 EU/μg protein (below the level of detection)
  • Recovery from stock vial: >95%

Qkine animal origin-free DKK-1 is as biologically active as a comparable alternative mammalian expressed supplier protein

Quantitative luciferase reporter assay shows equivalent bioactivity of Qkine AOF DKK-1 and mammalian-expressed DKK-1. HEK293T cells were treated in triplicate with a serial dilution of DKK-1 and a standard concentration of Wnt-3a for 24 hours.

Protein background

Dickkopf-related protein 1 (DKK-1) is a protein integral to the regulation of the Wnt signaling pathway and plays a pivotal role in embryonic development, tissue homeostasis, and various pathological conditions, including cancer [1-4]. As a member of the DKK protein family alongside DKK-2, DKK-3, and DKK-4, DKK-1 was initially identified as a Xenopus head-forming molecule and functions as a potent antagonist of the Wnt signaling pathway  [1].

With cell culture application, DKK1 is widely used for orchestrating cell fate decisions, self-renewal, and differentiation [5-6]. Its addition to the cell culture medium facilitates the binding to LDL receptor-related proteins 5 and 6 (LRP5/6) co-receptors, thereby inhibiting the activation of the canonical Wnt/β-catenin pathway  [7-8]. This interference proves instrumental in maintaining pluripotency, particularly by finely regulating the equilibrium between self-renewal and differentiation in embryonic stem cells (ESCs) [9].

The versatile utility of DKK-1 extends to the directed differentiation of induced pluripotent stem cells (iPSCs) into specific lineages, including neural differentiation, where it serves to promote the development of neural lineages [10]. Additionally, DKK-1 guides osteogenic differentiation of mesenchymal stem cells (MSCs), offering implications for bone tissue engineering and other related applications [11].

In the context of disease modeling in vitro, DKK1 finds application in mimicking conditions associated with dysregulated Wnt signaling pathways, as seen in certain cancers exhibiting aberrant Wnt expression, such as esophageal squamous cell carcinomas and hormone-resistant breast cancers [12].

Further insights into the regulatory mechanisms of DKK1 and its familial counterpart DKK-4 underscore their significant roles in modulating the Wnt/β-catenin signaling pathway. This pathway involves the interaction of Wnt ligands with the seven-transmembrane receptor Frizzled, along with co-receptors LRP5 and LRP6. DKK-1 forms inhibitory complexes with LRP5 and LRP6, as well as another receptor, Kremen, leading to endocytosis of this complex and subsequent removal of LRP5 and LRP6 from the cell surface [13-14].

DKK1 protein exhibits a structured composition. It includes an N-terminal signal peptide directing its secretion, a conserved cysteine-rich domain (CRD) crucial for disulfide bond formation, and a linker connecting the CRD to the C-terminal region. This C-terminal region interacts with other proteins and is implicated in the overall conformation and function of DKK-1. Specific amino acid residues within the CRD and C-terminal regions are vital for DKK-1’s inhibitory effect on the Wnt signaling pathway [15].

Notably, DKK-1’s inhibition of the Wnt pathway proves indispensable for anterior development, disrupting posterior patterning in vertebrates. This is evident in mice lacking DKK1 expression, where a deficiency leads to the absence of head formation [2,16]. Collectively, these molecular and functional insights underscore DKK-1’s intricate role in cellular processes and its potential as a valuable tool in manipulating cellular behaviour in diverse experimental settings.

Background references

  1. Glinka, A. et al.Dickkopf-1 is a member of a new family of secreted proteins and functions in head induction. Nature 391, 357–362 (1998). https://doi.org/10.1038/34848
  2. Grotewold, L., Theil, T. & Rüther, U. Expression pattern of Dkk-1 during mouse limb development. Mechanisms of Development 89, 151–153 (1999). https://doi.org/10.1016/s0925-4773(99)00194-x
  3. Yuan, S., Hoggard, N. K., Kantake, N., Hildreth, B. E. & Rosol, T. J. Effects of Dickkopf-1 (DKK-1) on Prostate Cancer Growth and Bone Metastasis. Cells 12, 2695 (2023). doi: 10.3390/cells12232695
  4. Fedi, P. et al.Isolation and Biochemical Characterization of the Human Dkk-1 Homologue, a Novel Inhibitor of Mammalian Wnt Signaling. Journal of Biological Chemistry 274, 19465–19472 (1999). doi: 10.1074/jbc.274.27.19465
  5. Zhang, J., Kang, N., Yu, X., Ma, Y. & Pang, X. Radial Extracorporeal Shock Wave Therapy Enhances the Proliferation and Differentiation of Neural Stem Cells by Notch, PI3K/AKT, and Wnt/β-catenin Signaling. Sci Rep 7, 15321 (2017). https://doi.org/10.1038/s41598-017-15662-5
  6. Li, M. et al.Perichondrium mesenchymal stem cells inhibit the growth of breast cancer cells via the DKK-1/Wnt/β-catenin signaling pathway. Oncology Reports 36, 936–944 (2016). doi: 10.3892/or.2016.4853
  7. Bafico, A., Liu, G., Yaniv, A., Gazit, A. & Aaronson, S. A. Novel mechanism of Wnt signalling inhibition mediated by Dickkopf-1 interaction with LRP6/Arrow. Nat Cell Biol 3, 683–686 (2001). doi: 10.1038/35083081
  8. Kulkarni, N. H. et al. Effects of parathyroid hormone on Wnt signaling pathway in bone. J of Cellular Biochemistry 95, 1178–1190 (2005). doi: 10.1002/jcb.20506
  9. Zovoilis, A., Smorag, L., Pantazi, A. & Engel, W. Members of the miR-290 cluster modulate in vitro differentiation of mouse embryonic stem cells. Differentiation 78, 69–78 (2009). doi: 10.1016/j.diff.2009.06.003
  10. Kong, X. B. & Zhang, C. Dickkopf (Dkk) 1 promotes the differentiation of mouse embryonic stem cells toward neuroectoderm. In Vitro Cell.Dev.Biol.-Animal 45, 185–193 (2009). doi: 10.1007/s11626-008-9157-2
  11. Liu, N. et al.High levels of β‐catenin signaling reduce osteogenic differentiation of stem cells in inflammatory microenvironments through inhibition of the noncanonical Wnt pathway. J of Bone & Mineral Res 26, 2082–2095 (2011). https://doi.org/10.1002/jbmr.440
  12. Browne, A. J. et al.p38 MAPK regulates the Wnt inhibitor Dickkopf-1 in osteotropic prostate cancer cells. Cell Death Dis 7, e2119–e2119 (2016). https://doi.org/10.1038/cddis.2016.32
  13. Internalization of REIC/Dkk-3 protein by induced pluripotent stem cell-derived embryoid bodies and extra-embryonic tissues. Int J Mol Med 26, (2010). doi: 10.3892/ijmm_00000534
  14. González-Sancho, J. M. et al.The Wnt antagonist DICKKOPF-1 gene is a downstream target of β-catenin/TCF and is downregulated in human colon cancer. Oncogene 24, 1098–1103 (2005). https://doi.org/10.1038/sj.onc.1208303
  15. Krupnik, V. E. et al.Functional and structural diversity of the human Dickkopf gene family. Gene 238, 301–313 (1999). doi: 10.1016/s0378-1119(99)00365-0
  16. Semënov, M. V. et al.Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6. Current Biology 11, 951–961 (2001). doi: 10.1016/s0960-9822(01)00290-1