FPS/FES PROTO-ONCOGENE IN MYELOID CELL FUNCTION
FPS/FES 原癌基因在骨髓细胞功能中的作用
基本信息
- 批准号:3460356
- 负责人:
- 金额:$ 7.47万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1991
- 资助国家:美国
- 起止时间:1991-07-01 至 1996-06-30
- 项目状态:已结题
- 来源:
- 关键词:SDS polyacrylamide gel electrophoresis antibody biological signal transduction cell differentiation cell growth regulation cell transformation enzyme mechanism gene expression gene interaction immunofluorescence technique laboratory mouse laboratory rabbit leukocyte activation /transformation macrophage molecular cloning molecular genetics northern blottings oncogenes phosphorylation polymerase chain reaction protein structure function protein tyrosine kinase protooncogene radionuclides site directed mutagenesis suppressor mutations temperature sensitive mutant tissue /cell culture transfection western blottings
项目摘要
The c-fps/fes gene encodes a cytoplasmic tyrosine kinase that is
specifically expressed in myeloid cells, in particular in macrophages.
The long-term objective of this study is to understand the biological
role and mechanism of action of this gene, and the molecular basis of its
oncogenic potential.
We will investigate the possible role of c-fps/fes in signal
transduction by determining if its product undergoes any biochemical
changes (i.e. tyrosine phosphorylation and activation of enzymatic
activity) during myeloid cell differentiation and macrophage activation,
and by examining the biological and biochemical effects of reintroducing
biologically active fps/fes genes into these cells. The biochemical
parameters of c-fps/fes action will be dissected using temperature
sensitive and other mutants of c-fps/fes, which will be introduced into
myeloid cells capable of undergoing differentiation and maturation by
retroviral mediated gene transfer. These experiments should clarify the
biological functions of c-fps/fes and provide the means to identify
proliferation-, differentiation-, and maturation-specific substrates. We
will also generate antibodies against two previously identified
substrates of c-fps/fes, which will be used for their characterization
and molecular cloning.
We will identify cellular proteins that interact with c-fps/fes
kinase using purified c-fps/fes protein expressed in baculovirus, and
functional domains expressed in bacteria, as affinity reagents. These
proteins will also be used to generate specific monoclonal and polyclonal
antibodies, which will be used in conjunction with fps/fes mutants to
study functional interactions of c-fps/fes kinase with substrates and
other cellular proteins.
The c-fps/fes product has unique biological and biochemical
properties. The elucidation of its mechanism of action will shed light
on the role of tyrosine phosphorylation in myeloid cell differentiation
and macrophage activation. As macrophage activation plays a central role
in the immune response to infections, and as new experimental therapies
rely on the use of myeloid CSFs that utilize tyrosine phosphorylation
pathways to achieve differentiation of leukemic cells, the mechanisms
uncovered in these studies have broad potential clinical implications.
c-fps/fes基因编码一种胞质酪氨酸激酶,
在骨髓细胞中特异性表达,特别是在巨噬细胞中。
这项研究的长期目标是了解生物学
该基因的作用和作用机制,及其分子基础,
致癌潜力
我们将研究c-fps/fes在信号转导中的可能作用
通过确定其产物是否经历任何生物化学过程来进行转导
改变(即酪氨酸磷酸化和酶的激活)
活动)在骨髓细胞分化和巨噬细胞激活期间,
通过研究重新引入的生物学和生物化学效应,
将具有生物活性的FPS/FES基因导入这些细胞中。 生化
将使用温度来剖析C-FPS/FES动作的参数
敏感和其他突变体的c-fps/fes,这将被引入到
能够通过以下方式进行分化和成熟的骨髓细胞:
逆转录病毒介导的基因转移。 这些实验应该澄清
c-fps/fes的生物学功能,并提供鉴定
增殖、分化和成熟特异性底物。 我们
也会产生针对两种先前鉴定的
c-fps/fes的衬底,这将用于它们的表征
和分子克隆。
我们将鉴定与c-fps/fes相互作用的细胞蛋白质
使用在杆状病毒中表达的纯化的c-fps/fes蛋白的激酶,和
在细菌中表达的功能域,作为亲和试剂。 这些
蛋白质也将用于产生特异性单克隆和多克隆抗体
抗体,将与fps/fes突变体结合使用,
研究c-fps/fes激酶与底物功能相互作用,
其他细胞蛋白质。
c-fps/fes产品具有独特的生物和生化特性,
特性. 阐明其作用机制将有助于阐明
酪氨酸磷酸化在骨髓细胞分化中的作用
和巨噬细胞活化。 由于巨噬细胞活化在
在感染的免疫反应中,
依赖于利用酪氨酸磷酸化的髓样CSF的使用
途径,以实现白血病细胞的分化,机制
在这些研究中发现的具有广泛的潜在临床意义。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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RICARDO A FELDMAN其他文献
RICARDO A FELDMAN的其他文献
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{{ truncateString('RICARDO A FELDMAN', 18)}}的其他基金
Cellular Electrophysiology of Nicotine Addiction Clinical Phenotypes
尼古丁成瘾临床表型的细胞电生理学
- 批准号:
8420444 - 财政年份:2012
- 资助金额:
$ 7.47万 - 项目类别:
Cellular Electrophysiology of Nicotine Addiction Clinical Phenotypes
尼古丁成瘾临床表型的细胞电生理学
- 批准号:
8323034 - 财政年份:2012
- 资助金额:
$ 7.47万 - 项目类别:
FPS/FES PROTO-ONCOGENE IN MYELOID CELL FUNCTION
FPS/FES 原癌基因在骨髓细胞功能中的作用
- 批准号:
2096505 - 财政年份:1991
- 资助金额:
$ 7.47万 - 项目类别:
FPS/FES PROTO-ONCOGENE IN MYELOID CELL FUNCTION
FPS/FES 原癌基因在骨髓细胞功能中的作用
- 批准号:
3460358 - 财政年份:1991
- 资助金额:
$ 7.47万 - 项目类别:
ROLE OF FPS/FES PROTO-ONCOGENE IN MYELOID CELL FUNCTION
FPS/FES 原癌基因在骨髓细胞功能中的作用
- 批准号:
6172483 - 财政年份:1991
- 资助金额:
$ 7.47万 - 项目类别:
ROLE OF FPS/FES PROTO-ONCOGENE IN MYELOID CELL FUNCTION
FPS/FES 原癌基因在骨髓细胞功能中的作用
- 批准号:
2894903 - 财政年份:1991
- 资助金额:
$ 7.47万 - 项目类别:
ROLE OF FPS/FES PROTO-ONCOGENE IN MYELOID CELL FUNCTION
FPS/FES 原癌基因在骨髓细胞功能中的作用
- 批准号:
6897410 - 财政年份:1991
- 资助金额:
$ 7.47万 - 项目类别:
FPS/FES PROTO-ONCOGENE IN MYELOID CELL FUNCTION
FPS/FES 原癌基因在骨髓细胞功能中的作用
- 批准号:
2552663 - 财政年份:1991
- 资助金额:
$ 7.47万 - 项目类别:
ROLE OF FPS/FES PROTO-ONCOGENE IN MYELOID CELL FUNCTION
FPS/FES 原癌基因在骨髓细胞功能中的作用
- 批准号:
2696318 - 财政年份:1991
- 资助金额:
$ 7.47万 - 项目类别:
FPS/FES PROTO-ONCOGENE IN MYELOID CELL FUNCTION
FPS/FES 原癌基因在骨髓细胞功能中的作用
- 批准号:
2096506 - 财政年份:1991
- 资助金额:
$ 7.47万 - 项目类别:
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