TY - JOUR
T1 - Phosphorylation and inactivation of glycogen synthase kinase 3 by protein kinase A
AU - Fang, Xianjun
AU - Yu, Shuang Xing
AU - Lu, Yiling
AU - Bast, Robert C.
AU - Woodgett, James R.
AU - Mills, Gordon B.
PY - 2000/10/24
Y1 - 2000/10/24
N2 - 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 is inhibited through phosphorylation of serine 21 in GSK-3α and serine 9 in GSK-3β. These serine residues of GSK-3 have been previously identified as targets of protein kinase B (PKB/Akt), a serine/threonine kinase located downstream of phosphatidyl-inositol 3-kinase. Here, we show that serine 21 in GSK-3α and serine 9 in GSK-3β are also physiological substrates of cAMP-dependent protein kinase A. Protein kinase A physically associates with, phosphorylates, and inactivates both isoforms of GSK-3. The results indicate that depending on the stimulatory context, the activity of GSK-3 can be modulated either by growth factors that work through the phosphatidylinositol 3-kinase-protein kinase B cascade or by hormonal stimulation of G protein-coupled receptors that link to changes in intracellular cAMP levels.
AB - 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 is inhibited through phosphorylation of serine 21 in GSK-3α and serine 9 in GSK-3β. These serine residues of GSK-3 have been previously identified as targets of protein kinase B (PKB/Akt), a serine/threonine kinase located downstream of phosphatidyl-inositol 3-kinase. Here, we show that serine 21 in GSK-3α and serine 9 in GSK-3β are also physiological substrates of cAMP-dependent protein kinase A. Protein kinase A physically associates with, phosphorylates, and inactivates both isoforms of GSK-3. The results indicate that depending on the stimulatory context, the activity of GSK-3 can be modulated either by growth factors that work through the phosphatidylinositol 3-kinase-protein kinase B cascade or by hormonal stimulation of G protein-coupled receptors that link to changes in intracellular cAMP levels.
UR - http://www.scopus.com/inward/record.url?scp=12944250922&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=12944250922&partnerID=8YFLogxK
U2 - 10.1073/pnas.220413597
DO - 10.1073/pnas.220413597
M3 - Article
C2 - 11035810
AN - SCOPUS:12944250922
SN - 0027-8424
VL - 97
SP - 11960
EP - 11965
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 22
ER -