Phosphorylation and inactivation of glycogen synthase kinase 3 by protein kinase A

• DOI: 10.1073/pnas.220413597
• Publication Date: 2002-07-26T14:45:09Z
• Authors: Xianjun Fang; Shuang Xing Yu; Yiling Lu; Robert C. Bast; James R. Woodgett; Gordon B. Mills
• Keywords: MAP2K7; GSK3B; ASK1; Cyclin-dependent kinase 9; c-Raf; AKT3; Phosphorylase kinase

Glycogen synthase kinase 3 (GSK-3) is implicated in multiple biological processes including metabolism, gene expression, cell fate determination, proliferation, and survival. GSK-3 activity inhibited through phosphorylation of serine 21 GSK-3α 9 GSK-3β. These residues have been previously identified as targets protein B (PKB/Akt), a serine/threonine located downstream phosphatidylinositol 3-kinase. Here, we show that GSK-3β are also physiological substrates cAMP-dependent A. Protein A physically associates with, phosphorylates, inactivates both isoforms GSK-3. The results indicate depending on the stimulatory context, can be modulated either by growth factors work 3-kinase–protein cascade or hormonal stimulation G protein-coupled receptors link to changes intracellular cAMP levels.