論文 - 詳細
RRC ID | 41436 |
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著者 | Kubota Y, Tanaka T, Kitanaka A, Ohnishi H, Okutani Y, Waki M, Ishida T, Kamano H. |
タイトル | Src transduces erythropoietin-induced differentiation signals through phosphatidylinositol 3-kinase. |
ジャーナル | EMBO J |
Abstract |
In this study, we examined the molecular mechanism of erythropoietin-initiated signal transduction of erythroid differentiation through Src and phosphatidylinositol 3-kinase (PI3-kinase). Antisense oligonucleotides against src but not lyn inhibited the formation of erythropoietin-dependent colonies derived from human bone marrow cells and erythropoietin-induced differentiation of K562 human erythroleukaemia cells. Antisense p85alpha oligonucleotide or LY294002, a selective inhibitor of PI3-kinase, independently inhibited the formation of erythropoietin-dependent colonies. In K562 cells, Src associated with PI3-kinase in response to erythropoietin. Antisense src RNA expression in K562 cells inhibited the erythropoietin-induced activation of PI3-kinase and its association with erythropoietin receptor. PP1, a selective inhibitor of the Src family, reduced erythropoietin-induced tyrosine phosphorylation of erythropoietin receptor and its association with PI3-kinase in F-36P human erythroleukaemia cells. The coexpression experiments and in vitro kinase assay further demonstrated that Src directly tyrosine-phosphorylated erythropoietin receptor, and associated with PI3-kinase. In vitro binding experiments proved that glutathione S-transferase-p85alpha N- or C-terminal SH2 domains independently bound to erythropoietin receptor, which was tyrosine-phosphorylated by Src. Taken together, Src transduces the erythropoietin-induced erythroid differentiation signals by regulating PI3-kinase activity. |
巻・号 | 20(20) |
ページ | 5666-77 |
公開日 | 2001-10-15 |
DOI | 10.1093/emboj/20.20.5666 |
PMID | 11598010 |
PMC | PMC125681 |
MeSH | Androstadienes / pharmacology Animals Bone Marrow Cells / drug effects COS Cells Cell Differentiation / drug effects Cell Differentiation / physiology Chlorocebus aethiops Chromones / pharmacology Colony-Forming Units Assay Enzyme Activation / drug effects Enzyme Inhibitors / pharmacology Erythroid Precursor Cells / cytology Erythroid Precursor Cells / drug effects* Erythropoietin / pharmacology Erythropoietin / physiology* Gene Expression Regulation, Leukemic / drug effects Genes, src Humans K562 Cells / drug effects Macromolecular Substances Morpholines / pharmacology Neoplasm Proteins / physiology Oligonucleotides, Antisense / pharmacology Phosphatidylinositol 3-Kinases / physiology* Phosphorylation Protein Processing, Post-Translational / drug effects Proto-Oncogene Proteins pp60(c-src) / physiology* Receptors, Erythropoietin / drug effects* Receptors, Erythropoietin / physiology Recombinant Proteins Signal Transduction / physiology* Transfection Wortmannin src Homology Domains src-Family Kinases / physiology |
IF | 9.889 |
引用数 | 50 |
WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
リソース情報 | |
ヒト・動物細胞 | F-36P(RCB0775) |