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

Xianjun Fang, Shuang Xing Yu, Yiling Lu, Robert C. Bast, James R. Woodgett, Gordon Mills

Research output: Contribution to journalArticle

525 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)11960-11965
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number22
DOIs
StatePublished - Oct 24 2000
Externally publishedYes

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Glycogen Synthase Kinase 3
Cyclic AMP-Dependent Protein Kinases
Phosphorylation
Serine
Proto-Oncogene Proteins c-akt
Phosphatidylinositol 3-Kinase
Biological Phenomena
Protein-Serine-Threonine Kinases
G-Protein-Coupled Receptors
Phosphatidylinositols
Intercellular Signaling Peptides and Proteins
Protein Isoforms
Phosphotransferases
Gene Expression

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Phosphorylation and inactivation of glycogen synthase kinase 3 by protein kinase A. / Fang, Xianjun; Yu, Shuang Xing; Lu, Yiling; Bast, Robert C.; Woodgett, James R.; Mills, Gordon.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 97, No. 22, 24.10.2000, p. 11960-11965.

Research output: Contribution to journalArticle

Fang, Xianjun ; Yu, Shuang Xing ; Lu, Yiling ; Bast, Robert C. ; Woodgett, James R. ; Mills, Gordon. / Phosphorylation and inactivation of glycogen synthase kinase 3 by protein kinase A. In: Proceedings of the National Academy of Sciences of the United States of America. 2000 ; Vol. 97, No. 22. pp. 11960-11965.
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