Glycogen synthase kinase-3 (GSK-3) specifically phosphorylates glycogen synthase, a critical enzyme regulating glucose storage, and mediates insulin regulation of glycogen synthesis.(8) GSK-3β phosphorylates regulatory sites in the central region of APC. Binding of β-catenin to APC, marking β-catenin for destruction, is dependent on phosphorylation of APC by GSK-3β. Thus, GSK-3β may play a critical role in regulating β-catenin stability during development and tumor progression. It is responsible for rapid cyclin D1 turnover by phosphorylating it on Thr-286. It functions as a negative regulator of Wnt signaling during embryonic development and cell proliferation in adult tissues.
