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Phosphorylation by p38 MAPK as an alternative pathway for GSK3beta inactivation.

journal contribution
posted on 2023-06-08, 11:15 authored by Tina M Thornton, Gustavo Pedraza-Alva, Bin Deng, David WoodDavid Wood, Alexander Aronshtam, James L Clements, Guadalupe Sabio, Roger J Davis, Dwight E Matthews, Bradley Doble, Mercedes Rincon
Glycogen synthase kinase 3beta (GSK3beta) is involved in metabolism, neurodegeneration, and cancer. Inhibition of GSK3beta activity is the primary mechanism that regulates this widely expressed active kinase. Although the protein kinase Akt inhibits GSK3beta by phosphorylation at the N terminus, preventing Akt-mediated phosphorylation does not affect the cell-survival pathway activated through the GSK3beta substrate beta-catenin. Here, we show that p38 mitogen-activated protein kinase (MAPK) also inactivates GSK3beta by direct phosphorylation at its C terminus, and this inactivation can lead to an accumulation of beta-catenin. p38 MAPK-mediated phosphorylation of GSK3beta occurs primarily in the brain and thymocytes. Activation of beta-catenin-mediated signaling through GSK3beta inhibition provides a potential mechanism for p38 MAPK-mediated survival in specific tissues.

History

Publication status

  • Published

Journal

Science

ISSN

0036-8075

Issue

5876

Volume

320

Page range

667-670

Department affiliated with

  • Biochemistry Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-04-17

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