Abstract
Dorsal accumulation of beta-catenin in early Xenopus embryos is required for body axis formation. Recent evidence indicates that beta-catenin is dorsally stabilized by the localized inhibition of the kinase Xgsk-3, utilizing a novel Wnt ligand-independent mechanism. Using a two-hybrid screen, we identified GBP, a maternal Xgsk-3-binding protein that is homologous to a T cell protooncogene in three well-conserved domains. GBP inhibits in vivo phosphorylation by Xgsk-3, and ectopic GBP expression induces an axis by stabilizing beta-catenin within Xenopus embryos. Importantly, antisense oligonucleotide depletion of the maternal GBP mRNA demonstrates that GBP is required for the establishment of the dorsal-ventral axis in Xenopus embryos. Our results define a family of GSK-3-binding proteins with roles in development and cell proliferation.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Body Patterning / genetics*
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Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors*
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Carrier Proteins / genetics
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Carrier Proteins / physiology*
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Cloning, Molecular
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Cytoskeletal Proteins / biosynthesis
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Enzyme Inhibitors
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Glycogen Synthase Kinase 3
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Intracellular Signaling Peptides and Proteins
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Molecular Sequence Data
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Oocytes / chemistry
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Phosphorylation
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Protein Binding
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Proto-Oncogenes
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RNA, Messenger / analysis
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Recombinant Fusion Proteins
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Sequence Homology, Amino Acid
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Trans-Activators*
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Xenopus Proteins*
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Xenopus laevis / embryology*
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Xenopus laevis / genetics
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beta Catenin
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tau Proteins / metabolism
Substances
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CTNNB1 protein, Xenopus
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Carrier Proteins
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Cytoskeletal Proteins
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Enzyme Inhibitors
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Intracellular Signaling Peptides and Proteins
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PIAS1 protein, Xenopus
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RNA, Messenger
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Recombinant Fusion Proteins
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Trans-Activators
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Xenopus Proteins
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beta Catenin
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tau Proteins
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Calcium-Calmodulin-Dependent Protein Kinases
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Glycogen Synthase Kinase 3
Associated data
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GENBANK/AF062738
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GENBANK/AF062739