Dkk-1 can be immunoprecipitated as a protein of relative molecular mass 40,000 (Mr 40K) from the medium of oocytes injected with FLAG-tagged dkk-1 mRNA, indicating that Dkk-1 is indeed secreted. Dkk-1 also inhibits late Wnt signalling. DKK-1 as a treatment target for these related diseases would be a beneficial strategy. This protein is seen as a well-characterized antagonist of the canonical Wnt signaling via binding to LRP5/6 to inhibit the formation of the Wnt-induced Fz-LRP5/6 complex. The following is a brief introduction. The Wnt1 protein can bind to β-propeller1 of LRP5/6, and Wnt3 can bind to β-propeller3 of LRP5/6. Not only can DKK-1 bind to the first β-propeller of LRP5 and LRP6 to inhibit Wnt1 class signaling, but it can also bind to the third β-propeller to inhibit Wnt3a class signaling. DKK-1 can utilize coreceptors to enhance its inhibitory function. Research has suggested that DKK-1 also inhibits the non-canonical Wnt pathway when the JNK pathway is activated. It has been indicated that DKK-1 gene transgenic cells can suppress cell growth and induce apoptotic cell death in mesothelioma cells via the non-canonical Wnt pathway. In other words, DKK-1 is a comprehensive regulator of the Wnt pathway.

References

1.Glinka A,et al. Nature. 1998 Jan 22;391(6665):357-62. 2.Huang Y,et al. Life Sci. 2018 Sep 15;209:249-254.