Phosphorylation by p38 MAPK as an alternative pathway for GSK3β inactivation
Phosphorylation by p38 MAPK as an alternative pathway for GSK3β inactivation
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DOI：
10.1126/science.1156037
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发表时间：
2008-05-02
期刊：
影响因子：
56.9
通讯作者：
Rincon, Mercedes
中科院分区：
文献类型：
--
作者：
Thornton, Tina M.;Pedraza-Alva, Gustavo;Rincon, Mercedes
糖原合成酶激酶3 β (GSK3 β)参与代谢、神经变性和癌症。抑制GSK3 β活性是调节这种广泛表达的活性激酶的主要机制。虽然蛋白激酶Akt通过在N端磷酸化抑制GSK3 β，但阻止Akt介导的磷酸化并不影响通过GSK3 β底物β - catenin激活的细胞存活途径。在这里，我们发现p38丝裂原活化蛋白激酶（MAPK）也通过在其C端直接磷酸化使GSK3 β失活，这种失活可导致β -连环蛋白的积累。p38 MAPK介导的GSK3 β磷酸化主要发生在脑和胸腺细胞中。通过抑制GSK3 β激活β - catenin介导的信号，为p38 MAPK介导的特定组织存活提供了潜在的机制。
Glycogen synthase kinase 3 beta (GSK3 beta) is involved in metabolism, neurodegeneration, and cancer. Inhibition of GSK3 beta activity is the primary mechanism that regulates this widely expressed active kinase. Although the protein kinase Akt inhibits GSK3 beta by phosphorylation at the N terminus, preventing Akt- mediated phosphorylation does not affect the cell- survival pathway activated through the GSK3 beta substrate beta- catenin. Here, we show that p38 mitogen- activated protein kinase ( MAPK) also inactivates GSK3 beta by direct phosphorylation at its C terminus, and this inactivation can lead to an accumulation of beta- catenin. p38 MAPK- mediated phosphorylation of GSK3 beta occurs primarily in the brain and thymocytes. Activation of beta- catenin- mediated signaling through GSK3 beta inhibition provides a potential mechanism for p38 MAPK- mediated survival in specific tissues.