| Project/Area Number |
06044071
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
IKAWA Yoji Tokyo Medical and Dental University Medical Research Division Professor, 医学系研究科, 教授 (40085618)
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| Co-Investigator(Kenkyū-buntansha) |
ロングモア グレゴリー ワシントン大学, 医学部, 助教授
YAMAMURA Yasuko Tokyo Medical and Dental University Medical Research Division, 医学系研究所, 助手 (50146809)
LONGMORE Gregory D. Washington University School of Medicine
グレゴリー ロングモア ワシントン大学, 医学部, 助教授
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| Project Period (FY) |
1994 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 1995: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1994: ¥3,600,000 (Direct Cost: ¥3,600,000)
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| Keywords | Erythropoietin / Erythroid Progenitor Cells / Erythroleukemia / JAK Kinase / STAT Transcription Factor / Signal Transduction / エリスロポエチン受容体 / サイトカインレセプター |
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| Research Abstract |
JAK2 tyrosine kinase has been shown to be physically associated with the erythropoietin (EPO) receptor (EPOR) and activated to transmit EPO signal in non-erythroid cell-derived transfectants. Here, we examined tyrosine phosphorylation of JAKs in erythroid progenitor cells from enlarged spleens of the Friend virus-infected DBA/2 mice. Western blot analysis showed that JAK1 was constitutively tyrosine-phosphorylated but JAK2 was not. In addition, both JAK1 and JAK2 were constitutively tyrosine-phosphorylated in the cells of an erythroleukemia cell line, T3C1-2-O.These results suggest that not only JAK2 but also JAK1 may play an essential role in the downstream signaling through the EPOR.JAK3 is associated with the IL-2 receptor gamma chain which is a common subunit of the receptors for IL-2, IL-4, IL-7, IL-9, and IL-15, and activated with these cytokines. We found that JAK3 was associated with the EPOR and tyrosinephosphorylated following EPO stimulation in EPO-dependent transfectants de
… More
rived from an IL-2-dependent T cell line, suggesting that JAK3 is also involved in EPO signaling in the T cell background.
STAT transcription factors transmit cytokine signals to the nucleus downstream of JAKs. We found that only STAY5, one of six members of the STAT family, was activated in the erythroid cells and EPO-dependent T cell transfectants. STAT5 may play an essential role in the EPO specific signaling.
Constitutively activated mutant EPOR,EPOR (R129C), was expressed in pluripotent progenitor cells obtained from spleens of 5-flurouracil-treated mice. The developmental potential of the cells were examined in methylcellulose culture in the presence of IL-3 and SCF.Expression of EPOR (R129C) allowed erythroid development in mixed colonies in the absence of EPO but did not increase the percentage of erythroid colony in mixed colonies. The EPO/EPOR signaling may regulate development of erythroblasts from erythroid progenitors but may not induce differentiation toward erythroid progenitors from pluripotent progenitors. Less
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