Function and Biological Roles of the Dickkopf Family of Wnt Modulators

Oncogene. 2006 Dec 4;25(57):7469-81. doi: 10.1038/sj.onc.1210054.

Abstract

Dickkopf (Dkk) genes comprise an evolutionary conserved small gene family of four members (Dkk1-4) and a unique Dkk3-related gene, Dkkl1 (soggy). They encode secreted proteins that typically antagonize Wnt/beta-catenin signaling, by inhibiting the Wnt coreceptors Lrp5 and 6. Additionally, Dkks are high affinity ligands for the transmembrane proteins Kremen1 and 2, which also modulate Wnt signaling. Dkks play an important role in vertebrate development, where they locally inhibit Wnt regulated processes such as antero-posterior axial patterning, limb development, somitogenesis and eye formation. In the adult, Dkks are implicated in bone formation and bone disease, cancer and Alzheimer's disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Body Patterning
  • Cell Lineage
  • Conserved Sequence
  • Humans
  • Intercellular Signaling Peptides and Proteins / physiology*
  • LDL-Receptor Related Proteins / metabolism
  • Low Density Lipoprotein Receptor-Related Protein-6
  • Mice
  • Models, Biological
  • Neoplasms / metabolism
  • Signal Transduction
  • Wnt Proteins / metabolism
  • Wnt Proteins / physiology*
  • Xenopus
  • Xenopus Proteins / physiology*

Substances

  • DKK1 protein, human
  • Dkk1 protein, mouse
  • Intercellular Signaling Peptides and Proteins
  • LDL-Receptor Related Proteins
  • LRP6 protein, human
  • Low Density Lipoprotein Receptor-Related Protein-6
  • Lrp6 protein, mouse
  • Wnt Proteins
  • Xenopus Proteins
  • dkk1 protein, Xenopus