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The axis-inducing activity, stability, and subcellular distribution of beta-catenin is regulated in Xenopus embryos by glycogen synthase kinase 3.

The serine/threonine kinase Xgsk-3 and the intracellular protein beta-catenin are necessary for the establishment of the dorsal-ventral axis in Xenopus. Although genetic evidence from Drosophila indicates that Xgsk-3 is upstream of beta-catenin, direct interactions between these proteins have not been demonstrated. We demonstrate that phosphorylation of beta-catenin in vivo requires an in vitro amino-terminal Xgsk-3 phosphorylation site, which is conserved in the Drosophila protein armadillo. beta-catenin mutants lacking this site are more active in inducing an ectopic axis in Xenopus embryos and are more stable than wild-type beta-catenin in the presence of Xgsk-3 activity, supporting the hypothesis that Xgsk-3 is a negative regulator of beta-catenin that acts through the amino-terminal site. Inhibition of endogenous Xgsk-3 function with a dominant-negative mutant leads to an increase in the steady-state levels of ectopic beta-catenin, indicating that Xgsk-3 functions to destabilize beta-catenin and thus decrease the amount of beta-catenin available for signaling. The levels of endogenous beta-catenin in the nucleus increases in the presence of the dominant-negative Xgsk-3 mutant, suggesting that a role of Xgsk-3 is to regulate the steady-state levels of beta-catenin within specific subcellular compartments. These studies provide a basis for understanding the interaction between Xgsk-3 and beta-catenin in the establishment of the dorsal-ventral axis in early Xenopus embryos.

Pubmed ID: 8666229

Authors

  • Yost C
  • Torres M
  • Miller JR
  • Huang E
  • Kimelman D
  • Moon RT

Journal

Genes & development

Publication Data

June 15, 1996

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM07270
  • Agency: NICHD NIH HHS, Id: HD27262
  • Agency: NICHD NIH HHS, Id: HD29360

Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Calcium-Calmodulin-Dependent Protein Kinases
  • Cell Nucleus
  • Cytoskeletal Proteins
  • Embryo, Nonmammalian
  • Embryonic Development
  • Embryonic Induction
  • Gene Expression Regulation, Developmental
  • Glycogen Synthase Kinase 3
  • Glycogen Synthase Kinases
  • Molecular Sequence Data
  • Morphogenesis
  • Mutation
  • Phosphorylation
  • Signal Transduction
  • Trans-Activators
  • Xenopus
  • Xenopus Proteins
  • beta Catenin