Phosphorylation by p38 MAPK as an Alternative Pathway for GSK3β Inactivation

摘要

Glycogen synthase kinase 3p (GSK3p) is involved in metabolism, neurodegeneration, and cancer. Inhibition of GSK3P activity is the primary mechanism that regulates this widely expressed active kinase. Although the protein kinase Akt inhibits GSK3p by phosphorylation at the N terminus, preventing Akt-mediated phosphorylation does not affect the cell-survival pathway activated through the GSK3P substrate p-catenin. Here, we show that p38 mitogen-activated protein kinase (MAPK) also inactivates GSK3P by direct phosphorylation at its C terminus, and this inactivation can lead to an accumulation of p-catenin. p38 MAPK-mediated phosphorylation of GSK3P occurs primarily in the brain and thymocytes. Activation of p-catenin-mediated signaling through GSK3P inhibition provides a potential mechanism for p38 MAPK-mediated survival in specific tissues.