Glycogen synthase kinase-3β mutagenesis identifies a common binding domain for GBP and axin

Glycogen synthase kinase-3β (GSK-3) is a key downstream target of Wnt signaling and is regulated by its interactions with activating and inhibitory proteins. We and others have shown that GSK-3 activity toward nonprimed substrates is regulated in part through a competition between its activating (Axin) and inhibitory (GBP/FRAT) binding partners. Here we use a reverse two-hybrid screen to identify mutations in GSK-3 that alter binding to GBP and Axin. We find that these mutations overlap and propose that GBP and Axin compete for binding to the same region of GSK-3. We use these mutations to examine the ability of GSK-3 to block eye, development in Xenopus embryos and suggest that GSK-3 regulates eye development through a non-Wnt pathway.