Report

Phosphorylation by p38 MAPK as an Alternative Pathway for GSK3β Inactivation

Science  02 May 2008:
Vol. 320, Issue 5876, pp. 667-670
DOI: 10.1126/science.1156037

You are currently viewing the abstract.

View Full Text

Via your Institution

Log in through your institution

Log in through your institution


Abstract

Glycogen synthase kinase 3β (GSK3β) is involved in metabolism, neurodegeneration, and cancer. Inhibition of GSK3β activity is the primary mechanism that regulates this widely expressed active kinase. Although the protein kinase Akt inhibits GSK3β by phosphorylation at the N terminus, preventing Akt-mediated phosphorylation does not affect the cell-survival pathway activated through the GSK3β substrate β-catenin. Here, we show that p38 mitogen-activated protein kinase (MAPK) also inactivates GSK3β by direct phosphorylation at its C terminus, and this inactivation can lead to an accumulation of β-catenin. p38 MAPK–mediated phosphorylation of GSK3β occurs primarily in the brain and thymocytes. Activation of β-catenin–mediated signaling through GSK3β inhibition provides a potential mechanism for p38 MAPK–mediated survival in specific tissues.

    View Full Text

    Cited By...