RRC ID |
39251
|
著者 |
Okajima Y, Matsumura I, Nishiura T, Hashimoto K, Yoshida H, Ishikawa J, Wakao H, Yoshimura A, Kanakura Y, Tomiyama Y, Matsuzawa Y.
|
タイトル |
Insulin-like growth factor-I augments erythropoietin-induced proliferation through enhanced tyrosine phosphorylation of STAT5.
|
ジャーナル |
J Biol Chem
|
Abstract |
Insulin-like growth factor (IGF-I) is known to synergistically stimulate the proliferation of hematopoietic cells in combination with other hematopoietic growth factors. However, the precise mechanism underlying the cooperative effects of IGF-I is unknown. In a human interleukin-3 or erythropoietin (EPO)-dependent cell line, F-36P, IGF-I alone failed to stimulate DNA synthesis but did augment the EPO-dependent DNA synthesis of F-36P cells. The treatment of F-36P cells with a combination of EPO and IGF-I (EPO/IGF-I) was found to enhance EPO-induced tyrosine phosphorylation of STAT5, whereas IGF-I alone did not. Furthermore, c-CIS mRNA expression, one of the target molecules of STAT5, was more effectively induced by EPO/IGF-I than by EPO alone. To examine the mechanisms of the EPO- and EPO/IGF-I-induced proliferation of F-36P cells, we expressed dominant negative (dn) mutants of STAT5 and Ras in an inducible system. The EPO-induced DNA synthesis and the cooperative effect of EPO/IGF-I were significantly inhibited by the inducible expression of dn-STAT5 or dn-Ras. In addition, the inducible expression of dn-Ras abolished the IGF-I-enhanced tyrosine phosphorylation of STAT5. These results suggest that IGF-I may augment EPO-induced proliferation by enhancing tyrosine phosphorylation of STAT5 and raise the possibility that Ras may be involved in the augmentation of STAT5 tyrosyl phosphorylation.
|
巻・号 |
273(36)
|
ページ |
22877-83
|
公開日 |
1998-9-4
|
DOI |
10.1074/jbc.273.36.22877
|
PII |
S0021-9258(19)74934-5
|
PMID |
9722506
|
MeSH |
Cell Division / drug effects
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
Dose-Response Relationship, Drug
Drug Synergism
Erythropoietin / pharmacology*
Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
Humans
Insulin-Like Growth Factor I / pharmacology*
Interleukin-3 / pharmacology
Janus Kinase 2
Leukemia, Erythroblastic, Acute
Milk Proteins*
Mutation
Phosphorylation
Protein-Tyrosine Kinases / metabolism
Proto-Oncogene Proteins*
Recombinant Proteins / metabolism
STAT5 Transcription Factor
Signal Transduction
Stem Cell Factor / pharmacology
Trans-Activators / genetics
Trans-Activators / metabolism*
Transcriptional Activation
Tumor Cells, Cultured
Tyrosine / metabolism
ras Proteins / metabolism
|
IF |
4.238
|
引用数 |
27
|
WOS 分野
|
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
リソース情報 |
ヒト・動物細胞 |
F-36P(RCB0775) |