Phosphorylation by p38 MAPK as an alternative pathway for GSK3beta inactivation
Authors
Thornton, TinaPedraza-Alva, Gustavo
Deng, Bin
Wood, C. David
Aronshtam, Alexander
Clements, James L.
Sabio, Guadalupe
Davis, Roger J.
Matthews, Dwight E.
Doble, Bradley
Rincon, Mercedes
UMass Chan Affiliations
Program in Molecular MedicineDocument Type
Journal ArticlePublication Date
2008-05-02
Metadata
Show full item recordAbstract
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.Source
Science. 2008 May 2;320(5876):667-70. doi: 10.1126/science.1156037. Link to article on publisher's siteDOI
10.1126/science.1156037Permanent Link to this Item
http://hdl.handle.net/20.500.14038/28342PubMed ID
18451303Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1126/science.1156037