RRC ID |
62172
|
著者 |
Takahashi-Yanaga F, Shiraishi F, Hirata M, Miwa Y, Morimoto S, Sasaguri T.
|
タイトル |
Glycogen synthase kinase-3beta is tyrosine-phosphorylated by MEK1 in human skin fibroblasts.
|
ジャーナル |
Biochem Biophys Res Commun
|
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.
|
巻・号 |
316(2)
|
ページ |
411-5
|
公開日 |
2004-4-2
|
DOI |
10.1016/j.bbrc.2004.02.061
|
PII |
S0006291X04003195
|
PMID |
15020233
|
MeSH |
Active Transport, Cell Nucleus / drug effects
Butadienes / pharmacology
Cell Nucleus / metabolism
Cells, Cultured
Enzyme Inhibitors / pharmacology
Fibroblasts / drug effects
Fibroblasts / enzymology*
Glycogen Synthase Kinase 3 / chemistry
Glycogen Synthase Kinase 3 / metabolism*
Glycogen Synthase Kinase 3 beta
Humans
MAP Kinase Kinase 1
MAP Kinase Kinase 2
Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
Mitogen-Activated Protein Kinase Kinases / metabolism*
Nitriles / pharmacology
Phosphorylation
Protein-Tyrosine Kinases / antagonists & inhibitors
Protein-Tyrosine Kinases / metabolism
Skin / cytology
Tyrosine / metabolism*
|
IF |
2.985
|
リソース情報 |
ヒト・動物細胞 |
NB1RGB(RCB0222) |