Differential regulation of glycogen synthase kinase 3beta by insulin and Wnt signaling.
Glycogen synthase kinase 3beta (GSK3beta) is a key component in many biological processes including insulin and Wnt signaling. Since the activation of each signaling pathway results in a decrease in GSK3beta activity, we examined the specificity of their downstream effects in the same cell type. Insulin induces an increased activity of glycogen synthase but has no influence on the protein level of beta-catenin. In contrast, Wnt increases the cytosolic pool of beta-catenin but not glycogen synthase activity. We found that, unlike insulin, neither the phosphorylation status of the serine9 residue of GSK3beta nor the activity of protein kinase B is regulated by Wnt. Although the decrease in GSK3beta activity is required, GSK3beta may not be the limiting component for Wnt signaling in the cells that we examined. Our results suggest that the axin-conductin complexed GSK3beta may be dedicated to Wnt rather than insulin signaling. Insulin and Wnt pathways regulate GSK3beta through different mechanisms, and therefore lead to distinct downstream events.
University of California, San Francisco, Cancer Research Institute, San Francisco, California 94143-0128, USA.
V W
VW
Ding
R H
RH
Chen
F
F
McCormick
D019943:Amino Acid Substitution; D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002460:Cell Line; D017077:Culture Media, Conditioned; D003600:Cytosol / Q000201:enzymology; D006006:Glycogen Synthase / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D006801:Humans; D007328:Insulin / Q000494:pharmacology / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014162:Transfection; D051153:Wnt Proteins; D029961:Zebrafish Proteins
D017077:Culture Media, Conditioned; D007328:Insulin; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D006006:Glycogen Synthase; D011505:Protein-Tyrosine Kinases; D038341:Glycogen Synthase Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3