Secreted and transmembrane wnt inhibitors and activators

Cold Spring Harb Perspect Biol. 2013 Mar 1;5(3):a015081. doi: 10.1101/cshperspect.a015081.

Abstract

Signaling by the Wnt family of secreted glycoproteins plays important roles in embryonic development and adult homeostasis. Wnt signaling is modulated by a number of evolutionarily conserved inhibitors and activators. Wnt inhibitors belong to small protein families, including sFRP, Dkk, WIF, Wise/SOST, Cerberus, IGFBP, Shisa, Waif1, APCDD1, and Tiki1. Their common feature is to antagonize Wnt signaling by preventing ligand-receptor interactions or Wnt receptor maturation. Conversely, the Wnt activators, R-spondin and Norrin, promote Wnt signaling by binding to Wnt receptors or releasing a Wnt-inhibitory step. With few exceptions, these antagonists and agonists are not pure Wnt modulators, but also affect additional signaling pathways, such as TGF-β and FGF signaling. Here we discuss their interactions with Wnt ligands and Wnt receptors, their role in developmental processes, as well as their implication in disease.

Publication types

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

MeSH terms

  • Animals
  • Embryonic Development / physiology*
  • Homeostasis / physiology*
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Membrane Glycoproteins / metabolism*
  • Models, Biological*
  • Protein Structure, Tertiary
  • Receptors, Wnt / metabolism*
  • Wnt Proteins / agonists
  • Wnt Proteins / antagonists & inhibitors
  • Wnt Proteins / metabolism*
  • Wnt Signaling Pathway / genetics*
  • Xenopus Proteins / metabolism

Substances

  • Intercellular Signaling Peptides and Proteins
  • Membrane Glycoproteins
  • Receptors, Wnt
  • Wnt Proteins
  • Xenopus Proteins
  • dkk1 protein, Xenopus