TY - JOUR
T1 - Glycogen synthase kinase-3β is tyrosine-phosphorylated by MEK1 in human skin fibroblasts
AU - Takahashi-Yanaga, Fumi
AU - Shiraishi, Fumie
AU - Hirata, Masato
AU - Miwa, Yoshikazu
AU - Morimoto, Sachio
AU - Sasaguri, Toshiyuki
N1 - Funding Information:
This work was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology (a Grant-in-Aid for Scientific Research).
PY - 2004/4/2
Y1 - 2004/4/2
N2 - 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.
AB - 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.
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U2 - 10.1016/j.bbrc.2004.02.061
DO - 10.1016/j.bbrc.2004.02.061
M3 - Article
C2 - 15020233
AN - SCOPUS:1542512457
SN - 0006-291X
VL - 316
SP - 411
EP - 415
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 2
ER -