Abstract
Using a yeast two-hybrid method, we identified a novel protein which interacts with glycogen synthase kinase 3beta (GSK-3beta). This protein had 44% amino acid identity with Axin, a negative regulator of the Wnt signaling pathway. We designated this protein Axil for Axin like. Like Axin, Axil ventralized Xenopus embryos and inhibited Xwnt8-induced Xenopus axis duplication. Axil was phosphorylated by GSK-3beta. Axil bound not only to GSK-3beta but also to beta-catenin, and the GSK-3beta-binding site of Axil was distinct from the beta-catenin-binding site. Furthermore, Axil enhanced GSK-3beta-dependent phosphorylation of beta-catenin. These results indicate that Axil negatively regulates the Wnt signaling pathway by mediating GSK-3beta-dependent phosphorylation of beta-catenin, thereby inhibiting axis formation.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing*
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Amino Acid Sequence
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Animals
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Axin Protein
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Body Patterning*
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Cytoskeletal Proteins / metabolism*
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Glycogen Synthase Kinase 3
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Glycogen Synthase Kinases
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Molecular Sequence Data
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Phosphorylation
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Protein Binding
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Proteins / genetics
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Proteins / metabolism*
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Repressor Proteins*
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Sequence Homology, Amino Acid
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Signal Transduction
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Trans-Activators*
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Wnt Proteins
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Xenopus / embryology
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Xenopus Proteins*
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Zebrafish Proteins
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beta Catenin
Substances
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AXIN2 protein, Xenopus
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Adaptor Proteins, Signal Transducing
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Axin Protein
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CTNNB1 protein, Xenopus
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Carrier Proteins
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Cytoskeletal Proteins
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Proteins
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Repressor Proteins
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Trans-Activators
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Wnt Proteins
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Xenopus Proteins
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Zebrafish Proteins
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axin1 protein, Xenopus
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beta Catenin
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wnt8a protein, zebrafish
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Glycogen Synthase Kinases
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Calcium-Calmodulin-Dependent Protein Kinases
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Glycogen Synthase Kinase 3