GBP, an inhibitor of GSK-3, is implicated in Xenopus development and oncogenesis.
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.
Yost
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Department of Biochemistry, University of Washington, Seattle 98195-7350, USA.
Farr
G H
GH
Pierce
S B
SB
Ferkey
D M
DM
Chen
M M
MM
Kimelman
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D
D000595:Amino Acid Sequence; D000818:Animals; D019521:Body Patterning / Q000235:genetics*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000096:biosynthesis; D004791:Enzyme Inhibitors; D038362:Glycogen Synthase Kinase 3; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009865:Oocytes / Q000737:chemistry; D010766:Phosphorylation; D011485:Protein Binding; D011519:Proto-Oncogenes; D012333:RNA, Messenger / Q000032:analysis; D011993:Recombinant Fusion Proteins; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators; D029867:Xenopus Proteins; D014982:Xenopus laevis / Q000196:embryology* / Q000235:genetics; D051176:beta Catenin; D016875:tau Proteins / Q000378:metabolism
C495266:CTNNB1 protein, Xenopus; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; C112892:PIAS1 protein, Xenopus; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D029867:Xenopus Proteins; D051176:beta Catenin; D016875:tau Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3