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Updated: Aug 13, 2026

Induction and Analysis of Epithelial to Mesenchymal Transition
Published on: August 27, 2013
Glycogen synthase kinase-3beta is tyrosine-phosphorylated by MEK1 in human skin fibroblasts
Fumi Takahashi-Yanaga1, Fumie Shiraishi, Masato Hirata
1Department of Clinical Pharmacology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. yanaga@clipharm.med.kyushu-u.ac.jp
Abstract:
Glycogen synthase kinase-3beta (GSK-3beta) can be associated with several proteins in cell. We analyzed the immunoprecipitates by an anti-GSK-3beta antibody from cell lysate of human fibroblasts and found that this protein was co-precipitated with mitogen-activated protein kinase kinase (MEK1/2). U0126, a MEK1/2 inhibitor, inhibited tyrosine phosphorylation of GSK-3beta, suggesting that MEK1/2 was involved in the phosphorylation of Tyr(216) in GSK-3beta. In vitro kinase assay was carried out using a recombinant human active MEK1 and we found that GSK-3beta was phosphorylated on Tyr(216) by this kinase in a dose- and time-dependent manner. Further, the pretreatment of fibroblasts with U0126 inhibited serum-induced nuclear translocation of GSK-3beta. These results suggested that MEK1/2 induces tyrosine phosphorylation of GSK-3beta and this cellular event might induce nuclear translocation of GSK-3beta. This is the first report to suggest that MEK1/2 phosphorylates not only ERK1/2 but also GSK-3beta.
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