Glycogen synthase kinase-3β is tyrosine-phosphorylated by MEK1 in human skin fibroblasts

Fumi Takahashi-Yanaga, Fumie Shiraishi, Masato Hirata, Yoshikazu Miwa, Sachio Morimoto, Toshiyuki Sasaguri

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46 Citations (Scopus)


Glycogen synthase kinase-3β (GSK-3β) can be associated with several proteins in cell. We analyzed the immunoprecipitates by an anti-GSK-3β 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-3β, suggesting that MEK1/2 was involved in the phosphorylation of Tyr216 in GSK-3β. In vitro kinase assay was carried out using a recombinant human active MEK1 and we found that GSK-3β was phosphorylated on Tyr216 by this kinase in a dose- and time-dependent manner. Further, the pretreatment of fibroblasts with U0126 inhibited serum-induced nuclear translocation of GSK-3β. These results suggested that MEK1/2 induces tyrosine phosphorylation of GSK-3β and this cellular event might induce nuclear translocation of GSK-3β. This is the first report to suggest that MEK1/2 phosphorylates not only ERK1/2 but also GSK-3β.

Original languageEnglish
Pages (from-to)411-415
Number of pages5
JournalBiochemical and Biophysical Research Communications
Issue number2
Publication statusPublished - Apr 2 2004

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


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