title: Secreted and transmembrane wnt inhibitors and activators.
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.
authors.affiliation: Division of Molecular Embryology, DKFZ-ZMBH Alliance, DKFZ, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
authors.forename: Cristina-Maria
authors.initials: CM
authors.lastname: Cruciat
authors.forename: Christof
authors.initials: C
authors.lastname: Niehrs
mesh_terms: D000818:Animals; D047108:Embryonic Development / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008954:Models, Biological; D017434:Protein Structure, Tertiary; D060490:Receptors, Wnt / Q000378:metabolism*; D051153:Wnt Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000235:genetics*; D029867:Xenopus Proteins / Q000378:metabolism
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D060490:Receptors, Wnt; D051153:Wnt Proteins; D029867:Xenopus Proteins; C110182:dkk1 protein, Xenopus