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).

在这个项目中，我们澄清了以下几点：1.Stat1和Stat3被促红细胞生成素（EPO）激活，并在EPO诱导的红细胞分化中充当负调节因子（JBC 272：16507，1997；Blood 92：462，1998）。 2.酪氨酸激酶Fes和JAK2激活Stat1和Stat3（手稿3.Stat3参与红细胞生成和巨核细胞生成中骨髓抑制的恢复（手稿正在准备中）。4． Stat3对血小板生成素（TPO）诱导的巨核细胞分化有负面影响（手稿正在准备中）。5． EPO和TPO信号通路之间存在串扰（手稿正在准备中）。6．丝裂原激活蛋白激酶、Erk-1 和 Erk-2 可能是细胞命运决定向红系和巨核细胞谱系的关键因素（Int. Hematol.，出版中）。6． EPO 受体和GATA-1 在红白血病细胞中高度表达(Exp. Hematol. 26: 1148, 1998)。7． FKHRL1 是 EPO 信号转导中 PI3K-Akt 激活途径的下游靶分子之一（新闻中的血液）。

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。

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。”

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。

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。”