Secreted and transmembrane wnt inhibitors and activators

• Published in: Cold Spring Harbor perspectives in biology Vol. 5; no. 3; p. a015081
• Main Authors: Cruciat, Cristina-Maria, Niehrs, Christof
• Format: Journal Article
• Language: English
• Published: United States Cold Spring Harbor Laboratory Press 01.03.2013
• Subjects: 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
• ISSN: 1943-0264; 1943-0264
• DOI: 10.1101/cshperspect.a015081

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.