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

  • Yost C
  • Torres M
  • Miller J
 et al. 
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The serine/threonine kinase Xgsk-3 and the intracellular protein β-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 β-catenin, direct interactions between these proteins have not been demonstrated. We demonstrate that phosphorylation of β-catenin in vivo requires an in vitro amino-terminal Xgsk-3 phosphorylation site, which is conserved in the Drosophila protein armadillo. β-Catenin mutants lacking this site are more active in inducing an ectopic axis in Xenopus embryos and are more stable than wild-type β-catenin in the presence of Xgsk-3 activity, supporting the hypothesis that Xgsk-3 is a neg. regulator of β-catenin that acts through the amino-terminal site. Inhibition of endogenous Xgsk-3 function with a dominant-neg. mutant leads to an increase in the steady-state levels of ectopic β-catenin, indicating that Xgsk-3 functions to destabilize β-catenin and thus decrease the amt. of β-catenin available for signaling. The levels of endogenous β-catenin in the nucleus increases in the presence of the dominant-neg. Xgsk-3 mutant, suggesting that a role of Xgsk-3 is to regulate the steady-state levels of β-catenin within specific subcellular compartments. These studies provide a basis for understanding the interaction between Xgsk-3 and β-catenin in the establishment of the dorsal-ventral axis in early Xenopus embryos. [on SciFinder(R)]

Author-supplied keywords

  • Wnt signaling
  • Xenopus development
  • Xgsk-3
  • axis formation
  • beta-Catenin
  • phosphorylation

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  • Cynthia Yost

  • Monica Torres

  • Jeffrey R Miller

  • Eugene Huang

  • David Kimelman

  • Randall T Moon

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