Dickkopf
Dickkopf (Dkk) is a negative regulator of Wnt signaling (Glinka, 1998; Niehrs, 1999) The Dkk protein is secreted and rich in cysteines. Dkk does not bind to Wnt but interacts with the Wnt co-receptor LRP (Mao, 2001; Bafico, 2001, Semenov, 2001; reviewed in Nusse, 2001. It also binds to a receptor called Kremen, resulting in down-regulation of LRP from the cells surface (Mao, 2002).
There are 4 Dkk members in the human genome. They have different activities; some do NOT inhibit Wnt signaling (Wu, 2000) This can sometimes be explained by the absence or presence of specific Kremen molecules; Kremen2 promotes Dkk2 activity (Mao and Niehrs, 2003)
While there are no known Drosophila or C. elegans homologs of Dkk, the diploblast Hydra has Dkk which antagonizes Wnt signaling (Guder, 2006, Augustin 2006)
Gene |
Human (HGNC) |
Mouse |
Xenopus |
|---|---|---|---|
| Dkk1 | DKK1 | Dkk1, Head Phenotype of KO | Xenopus Dkk1 |
| Dkk2 | DKK2 | Bone phenotype (Li, 2005) | |
| Dkk3 | DKK3 | frequency of NK cells Barrantes, 2006 | |
| Dkk4 | DKK4 |
The structure of Dkk bound to the LRP receptor has been established (Ahn et al, 2011, Cheng et al, 2011)
