Glycogen synthase kinase-3 beta mutagenesis identifies a common binding domain for GBP and Axin.
Glycogen synthase kinase-3 beta (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 non-primed 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.
Ferkey
Denise M
DM
Department of Biochemistry and Center for Developmental Biology, University of Washington, Seattle, Washington 98195-7350, USA.
Kimelman
David
D
D019943:Amino Acid Substitution; D000818:Animals; D060466:Axin Protein; D001665:Binding Sites; D001757:Blastomeres / Q000502:physiology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D051379:Mice; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D010750:Phosphoproteins / Q000378:metabolism*; D010940:Plant Proteins; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins; D014981:Xenopus / Q000196:embryology; D029867:Xenopus Proteins
D060466:Axin Protein; D002352:Carrier Proteins; D010750:Phosphoproteins; D010940:Plant Proteins; D011506:Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D029867:Xenopus Proteins; C555454:axin1 protein, Xenopus; C099131:gibberellin-binding phosphoprotein, plant; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3