DKK1 (human, recombinant)

Dickkopf-related protein 1 (DKK1) is a glycoprotein and a member of the DKK family of proteins.¹ DKK1 contains a signal sequence and N- and C-terminal conserved cysteine-rich domains connected by a non-conserved linker region. The C-terminal domain contains a colipase fold domain that is sufficient for its biological activity. DKK1 is a secretory protein that is expressed in osteoblasts, osteocytes, skin, placenta, prostate, and platelets.² It binds to lipoprotein receptor-related protein 5/6 (LRP5/6) to prevent it from forming a β-catenin-stabilizing complex with Wnt and Frizzled, thus inactivating Wnt-β-catenin signaling. In the presence of the DKK1 co-receptor Kremen, LRP6 is endocytosed to prevent its interaction with Wnt and Frizzled. DKK1 is also a target of the β-catenin-TCF transcription factor complex forming a negative feedback loop for Wnt signaling.³ Dkk1 knockout in mice is embryonic lethal with embryos lacking anterior head structures, as well as having ectopic and fused digits and fused vertebrae.⁴ Mice heterozygous for Dkk1 have increased bone density, and overexpression of Dkk1 in mice leads to osteopenia.¹ DKK1 expression is increased in a variety of cancers and plasma levels are correlated with the development of osteolytic lesion formation in patients with multiple myeloma.^1,5 Activation of DKK1 in cancer cells in vitro and in vivo can inhibit growth, however, DKK1 inhibition can reduce tumor growth in certain mouse xenograft models, suggesting a cell- or tissue-specific effect.^5,6 DKK1 expression is increased in the brain of Alzheimer’s disease mouse models, cerebrospinal fluid and plasma of patients with Alzheimer’s disease, and in postmortem brain derived from Alzheimer’s disease patients.⁷ Cayman’s DKK1 (human, recombinant) protein can be used for cell-based assay applications. This protein consists of 235 amino acids, has a calculated molecular weight of 25.8 kDa, and a predicted N-terminus of Thr32 or Ser35 after signal peptide cleavage. By SDS-PAGE, under reducing conditions, the apparent molecular mass of the protein is approximately 45 kDa due to glycosylation.

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1. Nierhs, C. Function and biological roles of the Dickkopf family of Wnt modulators. Oncogene 25(57), 7469-7481 (2006).

2. Ke, H.Z., Richards, W.G., Li, X., et al. Sclerostin and Dickkopf-1 as therapeutic targets in bone diseases. Endocr. Rev. 33(5), 747-783 (2012).

3. Niida, A., Hiroko, T., Kasai, M., et al. DKK1, a negative regulator of Wnt signaling, is a target of the β-catenin/TCF pathway. Oncogene 23(52), 8520-8526 (2004).

4. Mukhopadhyay, M., Shtrom, S., Rodriguez-Esteban, C., et al. Dickkopf1 is required for embryonic head induction and limb morphogenesis in the mouse. Dev. Cell 1(3), 423-434 (2001).

5. Menezes, M.E., Devine, D.J., Shevde, L.A., et al. Dickkopf1: A tumor suppressor or metastasis promoter? Int. J. Cancer 130(7), 1477-1483 (2012).

6. Mazon, M., Masi, D., and Carreau, M. Modulating Dickkopf-1: A strategy to monitor or treat cancer? Cancers (Basel) 8(7), 62 (2016).

7. Ren, C., Gu, X., Li, H., et al. The role of DKK1 in Alzheimer’s disease: A potential intervention point of brain damage prevention? Pharmacol. Res. 144, 331-335 (2019).