論文 - 詳細
RRC ID | 1345 |
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著者 | Kawano T, Horiguchi-Yamada J, Iwase S, Furukawa Y, Kano Y, Yamada H. |
タイトル | Inactivation of ERK accelerates erythroid differentiation of K562 cells induced by herbimycin A and STI571 while activation of MEK1 interferes with it. |
ジャーナル | Mol Cell Biochem |
Abstract |
K562 cells contain a Bcr-Abl chimeric gene and differentiate into various lineages in response to different inducers. We studied the role of the mitogen-activated protein kinase (MAPK) kinase 1 (MEK1)/extracellular signal-regulated kinase (ERK) pathway during the erythroid differentiation of K562 cells induced by tyrosine kinase inhibitors (herbimycin A or STI571), using genetically modified cells (constitutively MEK1-activated K562: K562/MEK1, and inducible ERK-inactivated K562: K562/CL100). Basal expression of glycophorin A was markedly reduced in K562/MEK1 cells compared with that in parental cells, while it was augmented in K562/CL100 cells. Herbimycin A and STI571 differentiated K562 cells accompanying with the transient down-regulated ERK. Moreover, the erythroid differentiation was markedly suppressed in K562/MEK1 cells, and early down-regulation of ERK activity was not observed in these cells. In contrast, the induction of ERK-specific phosphatase in K562/CL100 cells potentiated erythroid differentiation. Once the phosphatase was induced, the initial ERK activity became repressed and its early down-regulation by the inhibition of Bcr-Abl was marked and prolonged. These results demonstrate that the erythroid differentiation of K562 cells induced by herbimycin A or STI571 requires the down-regulation of MEK1/ ERK pathway. |
巻・号 | 258(1-2) |
ページ | 25-33 |
公開日 | 2004-3-1 |
DOI | 10.1023/b:mcbi.0000012830.96393.b9 |
PMID | 15030167 |
MeSH | Benzamides Benzoquinones Cell Differentiation / drug effects* Enzyme Activation / drug effects Enzyme Inhibitors / pharmacology* Erythroblasts / cytology Erythroblasts / metabolism Extracellular Signal-Regulated MAP Kinases* / antagonists & inhibitors Extracellular Signal-Regulated MAP Kinases* / metabolism Fusion Proteins, bcr-abl / metabolism Glycophorins / biosynthesis Humans Imatinib Mesylate K562 Cells Lactams, Macrocyclic MAP Kinase Kinase 1* / antagonists & inhibitors MAP Kinase Kinase 1* / genetics MAP Kinase Kinase 1* / metabolism Piperazines / pharmacology* Protein Tyrosine Phosphatases / genetics Protein Tyrosine Phosphatases / metabolism Pyrimidines / pharmacology* Quinones / pharmacology* Recombinant Proteins / genetics Recombinant Proteins / metabolism Rifabutin / analogs & derivatives Signal Transduction / drug effects Transfection |
IF | 2.795 |
引用数 | 17 |
WOS 分野 | CELL BIOLOGY |
リソース情報 | |
ヒト・動物細胞 | K562(RCB0027) |