title: A model for signaling specificity of Wnt/Frizzled combinations through co-receptor recruitment.
abstract: Wnts control mammalian developmental morphogenesis and are critical for adult stem cell maintenance. Wnts initiate several intracellular signaling cascades, such as Wnt/β-catenin-, Wnt/Ca(2+)- and Wnt/ROR2-signaling. Signaling preference of Wnts for these various pathways is thought to depend on the repertoire of receptors present on recipient cells. Here, we propose a further refinement of this receptor model and hypothesize that Wnt signaling specificity depends on co-receptor recruitment upon binding of Wnt to Frizzled receptor molecules. In this model, recruitment of LRP5/6 leads to activation of Wnt/β-catenin signaling, whereas signaling through other pathways is mediated by recruiting ROR2.
authors.affiliation: Merck Research Laboratories, Molecular Pharmacology & DMPK, Oss, The Netherlands.
authors.forename: Folkert
authors.initials: F
authors.lastname: Verkaar
authors.forename: Guido J R
authors.initials: GJ
authors.lastname: Zaman
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D051157:Frizzled Receptors / Q000378:metabolism*; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000378:metabolism*; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000378:metabolism*; D011973:Receptors, LDL / Q000378:metabolism*; D015398:Signal Transduction; D051153:Wnt Proteins / Q000378:metabolism*
chemical_list: D051157:Frizzled Receptors; D026502:LDL-Receptor Related Proteins; C555482:LRP5 protein, human; C555475:LRP6 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D011973:Receptors, LDL; D051153:Wnt Proteins; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; D002118:Calcium