analysis of molecular mechanism of hematopoiesis and hematological disorders

造血及血液病分子机制分析

• 批准号: 09470233
• 负责人: KOMATSU Norio
• 金额: $ 8.06万
• 依托单位: Jich Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470233/
• 关键词: erythropoietin; transgenic mice; erythroid differentiation; UT-7; GATA-1; megakaryocytic differentiation; STAT 3; STAT 1; エリスロポエチン; トロンボポエチン; MAPキナーゼ; STAT蛋白; チロシンキナーゼ; 細胞周期; p21; WAF-1; 顆粒球・マクロファージコロニー刺激因子

In this project, we clarified several things as follows;1.Stat1 and Stat3 are activated by erythropoietin (EPO) and function as negative regulators in EPO-induced erythroid differentiation (JBC 272: 16507, 1997; Blood 92: 462, 1998).2.Tyrosine kinases Fes and JAK2 activates Stat1 and Stat3 (manuscript in preparation).3.Stat3 is involved in recovery from myelosupression in erythropoiesis and megakaryopoiesis (manuscript in preparation).4. Stat3 has a negative effect on thrombopoietin (TPO)-induced megakaryocytic differentiation (manuscript in preparation.).5. There is a crosstalk between EPO and TPO signaling pathways (manuscript in preparation).6. Mitogen-activated protein kinases, Erk-1 and Erk-2 functions as a possible key factor for cell fate determination toward erythroid and megakaryocytic lineages (Int. Hematol., in press).6. EPO receptor and GATA-1 are highly expressed in erythroleukemia cells (Exp. Hematol. 26: 1148, 1998).7. FKHRL1 is one of downstream target molecules of PI3K-Akt activation pathway in EPO signal transduction (Blood in press).

本课题主要阐明了以下几点：1. Stat 1和Stat 3被促红细胞生成素（EPO）激活，在EPO诱导的红系分化中起负调节作用（JBC 272：16507，1997; Blood 92：462,酪氨酸激酶Fes和JAK 2激活Stat 1和Stat 3 Stat 3参与红细胞生成和巨核细胞生成中骨髓抑制的恢复（手稿在准备中）。Stat 3对血小板生成素（TPO）诱导的巨核细胞分化有负面影响（手稿在准备中）。5. EPO和TPO信号通路之间存在串扰（手稿在准备中）.促分裂原活化蛋白激酶Erk-1和Erk-2作为细胞朝向红细胞和巨核细胞谱系的命运决定的可能的关键因子发挥作用（Int.Hematol.，6. EPO受体和加塔-1在红白血病细胞中高度表达（Exp.血液。26：1148，1998）。FKHRL 1是EPO信号转导中PI 3 K-Akt活化途径的下游靶分子之一（Blood in press）。

项目成果

Komatsu N., et al: "GATA-1 and erythropoietin receptor genes are highly expressed in erythroleukemia"Exp. Hematol.. 26. 1148-1154 (1998)

Komatsu N.等人：“GATA-1和促红细胞生成素受体基因在红白血病中高度表达”Exp。

Akimoto, T.: "The effect of erythropoietin on interleukin-1beta mediated increase in nitric oxide synthesis in vascular smooth muscle cells"J Hypertens. 17(in press). 1249-1256 (1999)

Akimoto, T.：“促红细胞生成素对白介素-1β 介导的血管平滑肌细胞一氧化氮合成增加的影响”J Hypertens。

Yamashita, Y., et al: "Tec and Jak2 kineses Cooperate to Mediate Cytokine-Driven Activation of c-fos Transcription"Blood. 91. 1496-1507 (1998)

Yamashita, Y. 等人：“Tec 和 Jak2 运动协同介导细胞因子驱动的 c-fos 转录激活”血液。

Kiroto K.: "A novel function of Stat3 and Stat3 in the erythropoietin-induced erythroid differentiation of a human leukemio cell line." Blood. 92. 462-417 (1998)

Kiroto K.：“Stat3 和 Stat3 在促红细胞生成素诱导的人类白血病细胞系红系分化中的新功能。”

Broudy VC: "Analysis of c-kit receptor dimerization by fluorescence energy transfer." Blood. 91. 898-906 (1998)

Broudy VC：“通过荧光能量转移分析 c-kit 受体二聚化。”