Figure 2.

Regulation of GSK-3β. GSK-3β is a multifunctional kinase that has a role in various signaling pathways that regulate cell fate. ZAK1 or Fyn can phosphorylate Tyr-216 which increases the GSK-3β activity. GSK-3β can phosphorylate downstream targets like β-catenin and degrade it through the ubiquitin-proteasome system. Akt and PKC on the other hand can attenuate GSK-3β enzymatic activity by phosphorylating Ser-9. Inhibition of GSK-3β activity therefore leads to stabilization and accumulation of β-catenin in the cytosol, which is shuttled into the nucleus where it functions to regulate gene expression. GSK-3β is also involved in cell cycle regulation through the phosphorylation of cyclin D1, which results in the rapid proteolytic turnover of cyclin D1 protein.