Abstract
In a recent issue of Nature, Hao et al. report an unexpected link between the secreted stem cell factor/Wnt agonist R-spondin and Wnt receptors through the transmembrane ZNRF3 protein, a RING finger ubiquitin ligase. ZNRF3 acts to turn over Frizzled and LRP6 receptors. R-spondin binds to ZNRF3, in addition to transmembrane LGR4/5 receptors, to antagonize degradation of the Wnt receptors by ZNRF3, thereby resulting in increased Frizzled and LRP6 levels and a greater Wnt response.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Frizzled Receptors / metabolism
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Humans
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Low Density Lipoprotein Receptor-Related Protein-6 / metabolism
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Protein Binding
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RNA Interference
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Receptors, Wnt / metabolism*
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Stem Cell Factor / metabolism
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Thrombospondins / metabolism
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Ubiquitin-Protein Ligases / antagonists & inhibitors
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Ubiquitin-Protein Ligases / genetics
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Ubiquitin-Protein Ligases / metabolism
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Wnt Proteins / agonists
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Wnt Proteins / metabolism
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Wnt Signaling Pathway*
Substances
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Frizzled Receptors
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LRP6 protein, human
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Low Density Lipoprotein Receptor-Related Protein-6
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RSPO1 protein, human
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Receptors, Wnt
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Stem Cell Factor
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Thrombospondins
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Wnt Proteins
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Ubiquitin-Protein Ligases
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ZNRF3 protein, human