Regulation of IL-3 and GM-CSF genes and their receptors
IL-3 和 GM-CSF 基因及其受体的调节
基本信息
- 批准号:04044054
- 负责人:
- 金额:$ 8.26万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for international Scientific Research
- 财政年份:1992
- 资助国家:日本
- 起止时间:1992 至 1994
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
1.Regulation of cytokine genes in T cells. Using human and mouse T cell clones with TH1, TH2, and TH0 phenotype, we have been working on the coordinate and differential expression of the IL-3, IL-4, IL-5 and GM-CSF genes. The CLE2/GC-box and CLE0 of the mouse GM-CSF promoter are essential for transcriptional activation in response to PMA and Ca ionophore. CLE2 defines a binding site for NF-kappaB.The major GC-box binding activity A1 was purified and was identified as Sp1. We purified a human NF-AT protein from activated Jurkat extract and showed that it strongly bound to the CLE0 within the GM-CSF promoter in association with AP1. We isolated a novel protein with zinc finger motifs which binds to the CT/GC-rich region of the IL-3 promoter. We also identified cis-regulatory elements within IL-5, IL-4 and IL-2 promoters. These works were done in collaboration with Drs.Naoko Arai and de Vries Jan in DNAX.2.Receptor and Signal transduction. We have been working on the structure and function of GM-CSF/IL-3 receptors. There are several signal pathways downstream of the GM-CSF receptor. The membrane proximal region of betac is essential for proliferation, c-myc and pim-1 induction and Jak2 association. The C-terminal region of betac is important for the suppression of apoptosis, Ras, Raf, MAPK activation and c-fos, c-jun induction. We have also shown that bone marrow cells derived from transgenic mice which constitutively express hGM-CSF receptor have the proliferative capacity to induce all the myeloid cell lineages in response to hGM-CSF.Furthermore, we have generated mice carrying a null mutation of betac and betaIL-3. betac mutant mice also showed lung pathology consisting of lymphocytic infiltration and areas resembling alveolar proteinosis. These works were done in collaboration with Dr.Atsushi Miyajima in DNAX and Dr.Ostertag Wolfram in Hamburg University.
1. T细胞中细胞因子基因的调节。使用具有TH 1、TH 2和TH 0表型的人和小鼠T细胞克隆,我们一直致力于IL-3、IL-4、IL-5和GM-CSF基因的协调和差异表达。小鼠GM-CSF启动子的CLE 2/GC-box和CLE 0是响应PMA和Ca离子载体的转录激活所必需的。CLE 2定义了NF-κ B的结合位点。纯化了主要的GC盒结合活性A1,并鉴定为Sp1。我们从活化的Jurkat提取物中纯化了一种人NF-AT蛋白,并表明它与AP 1相关的GM-CSF启动子内的CLE 0强烈结合。我们分离了一种新的蛋白质与锌指基序结合的CT/GC丰富的区域的IL-3启动子。我们还鉴定了IL-5、IL-4和IL-2启动子内的顺式调节元件。这些工作是与Naoko Arai和de弗里斯Jan博士在DNAX.2.受体和信号转导中合作完成的。我们一直在研究GM-CSF/IL-3受体的结构和功能。在GM-CSF受体下游存在几种信号通路。betac的膜近端区域对于增殖、c-myc和pim-1诱导以及Jak 2缔合是必需的。betac的C端区域在抑制细胞凋亡、Ras、Raf、MAPK激活以及c-fos、c-jun诱导中起重要作用。我们还表明,来自组成型表达hGM-CSF受体的转基因小鼠的骨髓细胞具有诱导所有髓系细胞谱系响应hGM-CSF的增殖能力。此外,我们已经产生了携带β c和β IL-3无效突变的小鼠。Betac突变小鼠还显示出由淋巴细胞浸润和类似肺泡蛋白沉积的区域组成的肺病理学。这些工作是与DNAX的宫岛敦博士和汉堡大学的奥斯特塔格·沃尔夫勒姆博士合作完成的。
项目成果
期刊论文数量(96)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Kinoshita,T.: "Regulation of Bcl-2 expression by oncogenic Ras protein in hemopoietic cells" Oncogene.(in press).
Kinoshita,T.:“造血细胞中致癌 Ras 蛋白对 Bcl-2 表达的调节”Oncogene。(出版中)。
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Koyano-Nakagawa,N.: "Molecular cloning of a novel human cDNA encoding a zinc finger protein..." Mol.Cell.Biol.14. 5099-5107 (1994)
Koyano-Nakakawa,N.:“编码锌指蛋白的新型人类 cDNA 的分子克隆……”Mol.Cell.Biol.14。
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Watanabe.S.: "Effects of prostaglandin E1 on Th0-type human T cell clones:modulation..." Int.Immunol.6. 523-532 (1994)
Watanabe.S.:“前列腺素 E1 对 Th0 型人类 T 细胞克隆的影响:调节……”Int.Immunol.6。
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Koyano-Nakagawa, N.: "Reconstitution of the functional GM-CSF promoter : Evidence for distinct..." Int.Immunology. 5. 345-352 (1993)
Koyano-Nakakawa, N.:“功能性 GM-CSF 启动子的重建:不同的证据......” Int.Immunology。
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- 影响因子:0
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Watanabe, S.: "Characterization of cis-regulatory elements of the c-myc promoter..." Mol.Biol.Cell.(in press).
Watanabe, S.:“c-myc 启动子的顺式调控元件的表征……”Mol.Biol.Cell.(正在印刷中)。
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ARAI Ken-ichi其他文献
ARAI Ken-ichi的其他文献
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{{ truncateString('ARAI Ken-ichi', 18)}}的其他基金
Joint study on DNA replication and checkpoint control
DNA复制和检查点控制的联合研究
- 批准号:
11694247 - 财政年份:1999
- 资助金额:
$ 8.26万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Studies on regulation of mitotic DNA replication and meiosis by novel Cdc7-related kinase complexes
新型Cdc7相关激酶复合物调控有丝分裂DNA复制和减数分裂的研究
- 批准号:
10480164 - 财政年份:1998
- 资助金额:
$ 8.26万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Analyses of cytokine gene expression by helper T cell subsets : role of NFAT-mediated gene activation and subset-specific regulatory mechanism.
辅助 T 细胞亚群的细胞因子基因表达分析:NFAT 介导的基因激活的作用和亚群特异性调节机制。
- 批准号:
08457103 - 财政年份:1996
- 资助金额:
$ 8.26万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Joint study on regulation of cell profferation by cytokines
细胞因子调控细胞增殖的联合研究
- 批准号:
07044230 - 财政年份:1995
- 资助金额:
$ 8.26万 - 项目类别:
Grant-in-Aid for international Scientific Research
Generation of disease model mice by the alteration of transcription factors regulating immune responses
通过改变调节免疫反应的转录因子产生疾病模型小鼠
- 批准号:
07557024 - 财政年份:1995
- 资助金额:
$ 8.26万 - 项目类别:
Grant-in-Aid for Scientific Research (A)
Development of high-level expression vectors in embryonic and hematopoietic stem cells and generati of GM-CSF and IL-3 of receptor transgenic mice
胚胎干细胞和造血干细胞高水平表达载体的研制及受体转基因小鼠GM-CSF和IL-3的产生
- 批准号:
04559003 - 财政年份:1992
- 资助金额:
$ 8.26万 - 项目类别:
Grant-in-Aid for Developmental Scientific Research (B)
Gene expression and DNA replication triggered by growth factors and their receptors
生长因子及其受体触发的基因表达和 DNA 复制
- 批准号:
02404086 - 财政年份:1990
- 资助金额:
$ 8.26万 - 项目类别:
Grant-in-Aid for General Scientific Research (A)
Denaturation and Its Regulation of Muscular Protein in Marine Animals induced by Storage and Processing as Foodstuff.
食品储存和加工引起的海洋动物肌肉蛋白变性及其调控。
- 批准号:
59470114 - 财政年份:1984
- 资助金额:
$ 8.26万 - 项目类别:
Grant-in-Aid for General Scientific Research (B)
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NHMRC Project Grants
Molecular cloning of IL-3 receptor-associated antigen
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08457198 - 财政年份:1996
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The Significance of IL-3 Receptor beta chain for FLT3-ITD Dependent Oncogeneic Signaling in AML
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