GBP, AN INHIBITOR OF GSK-3, IS IMPLICATED IN XENOPUS DEVELOPMENT AND ONCOGENESIS

Dorsal accumulation of beta-catenin in early Xenopus embryos is requir ed for body axis formation. Recent evidence indicates that beta-cateni n is dorsally stabilized by the localized inhibition of the kinase Xgs k-3, utilizing a novel Wnt ligand-independent mechanism. Using a two-h ybrid screen, we identified GBP, a maternal Xgsk-3-binding protein tha t is homologous to a T cell protooncogene in three well-conserved doma ins. GBP inhibits in vivo phosphorylation by Xgsk-3, and ectopic GBP e xpression induces an axis by stabilizing beta-catenin within Xenopus e mbryos. Importantly, antisense oligonucleotide depletion of the matern al GBP mRNA demonstrates that GBP is required for the establishment of the dorsal-ventral axis in Xenopus embryos. Our results define a fami ly of GSK-3-binding proteins with roles in development and cell prolif eration.