RAS GENES BY DOMINANT NEGATIVE MUTANTS
RAS GENES BY DOMINANT NEGATIVE MUTANTS
批准号:
2095478
负责人:
YU-WEN HWANG
金额:
$11.77万
依托单位国家:
美国
项目类别:
财政年份:
1990
资助国家:
美国
项目状态:
已结题
起止时间:
1990-12-15 至 1995-11-30
关键词:
PC12 cells autosomal dominant trait biological products biological signal transduction cell differentiation enzyme linked immunosorbent assay gene induction /repression gene interaction gene mutation genetic manipulation genetic promoter element guanine nucleotide binding protein microinjections microorganism genetics molecular cloning molecular genetics neurotrophic factors nucleic acid hybridization oncogenes protein sequence radionuclides tissue /cell culture transfection
中文摘要
研究表明,激活的ras基因在许多肿瘤的发生、发展中起着重要作用。
人类肿瘤的种类直接ras基因家族由三个
成员,H-ras,K-ras和N-ras。ras基因属于一组
这些蛋白质统称为鸟嘌呤核苷酸结合蛋白。
鸟嘌呤-核苷酸结合蛋白需要鸟嘌呤-核苷酸进行其
适当的功能,并共享其中的几个保守的功能。许多
鸟嘌呤-核苷酸结合蛋白参与转导刺激
因此,可以想象,ras基因可能是一种
产品具有相似的生物学作用。目前,我们所知不多,
ras基因的信号转导途径。除了明显的
在细胞增殖中的作用,ras基因也被证明可以诱导
某些细胞类型的终末分化,如大鼠嗜铬细胞瘤
细胞系PC 12,体外神经元细胞模型。
最近,我们描述了一类H-ras突变体,其可以显性地
抑制c-H-ras基因以及其他几种癌基因的作用,
例如SRC、FMS、SIS和FES。这种反式显性遗传的基础
抑制可能归因于基本元素的螯合
c-H-ras激活所必需的。这些变种人将提供一个
研究ras信号转导通路的有用工具
ras基因与其他癌基因的相互作用。我们提出
研究反式显性抑制的潜在机制,
也利用这些突变体的反式显性特性来研究
ras基因的生物学作用
1.我们将确定H-ras p2 l蛋白的物理需求,
反式显性抑制; 2.我们将确定K-ras(或
N-ras)c-H-ras和如前所述的其他癌基因上的突变体; 3.
我们将利用反式显性突变体作为亲和探针,
纯化与ras p2 l蛋白相互作用的元件; 4.我们将
研究ras p2 l蛋白在PC 12细胞分化中的作用
反式显性突变体
英文摘要
It has been demonstrated that activated ras genes play vital roles in many
types of human tumor. The immediate ras gene family consists of three
members, H-ras, K-ras and N-ras. The ras genes belong to a group of
proteins collectively called guanine-nucleotide binding proteins.
Guanine-nucleotide binding proteins require guanine-nucleotides for their
proper functions and share several conserved features among them. Many
guanine-nucleotide binding proteins are involved in transducing the stimuli
signals to their targets; therefore, it is conceivable that the ras gene
products have similar biological roles. At present, not much is known about
the signal transduction pathway of ras genes. In addition to their apparent
role in cell proliferation, ras genes also have been shown to induce
terminal differentiation in some cell types, such as rat pheochromocytoma
cell line PC12, a in vitro neuronal cell model.
Recently, we have described a class of H-ras mutants which can dominantly
suppress the action of the c-H-ras gene as well as several other oncogenes,
such as src, fms, sis and fes. The basis for this type of trans-dominant
suppression might be attributed to sequestering of the essential element
required for c-H-ras activation. These mutants will provide an extremely
valuable tool for investigating the signal transduction pathway of ras
genes and the interactions of ras genes with other oncogenes. We propose
to study the underlying mechanism of trans-dominant suppression and will
also utilize the trans-dominant properties of these mutants to study the
biological role of the ras genes.
1. We will determine the physical requirements of the H-ras p2l protein for
trans-dominant suppression; 2. we will determine the effects of K-ras (or
N-ras) mutants on c-H-ras and other oncogenes as mentioned previously; 3.
we will utilize the trans-dominant mutants as the affinity probe for
purifying the element that interacts with ras p2l protein and 4. we will
investigate the role of the ras p2l protein in differentiating PC12 cells
by trans-dominant mutants.
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会议论文
PROBING CELLULAR FUNCTIONS OF THE MINIBRAIN KINASE
-
批准号:6363443
-
项目类别:
-
资助金额:$21.18万
-
财政年份:2000
-
负责人:YU-WEN HWANG
-
依托单位:
PROBING CELLULAR FUNCTIONS OF THE MINIBRAIN KINASE
-
批准号:6027955
-
项目类别:
-
资助金额:$21.47万
-
财政年份:2000
-
负责人:YU-WEN HWANG
-
依托单位:
PROBING CELLULAR FUNCTIONS OF THE MINIBRAIN KINASE
-
批准号:6521258
-
项目类别:
-
资助金额:$21.82万
-
财政年份:2000
-
负责人:YU-WEN HWANG
-
依托单位:
PROBING CELLULAR FUNCTIONS OF THE MINIBRAIN KINASE
-
批准号:6637037
-
项目类别:
-
资助金额:$22.47万
-
财政年份:2000
-
负责人:YU-WEN HWANG
-
依托单位:
PROBING CELLULAR FUNCTIONS OF THE MINIBRAIN KINASE
-
批准号:6698536
-
项目类别:
-
资助金额:$23.15万
-
财政年份:2000
-
负责人:YU-WEN HWANG
-
依托单位:
BIOCHEMICAL CHARACTERIZATION OF THE MINIBRAIN GENE
-
批准号:2677047
-
项目类别:
-
资助金额:$8.15万
-
财政年份:1998
-
负责人:YU-WEN HWANG
-
依托单位:
BIOCHEMICAL CHARACTERIZATION OF THE MINIBRAIN GENE
-
批准号:2883167
-
项目类别:
-
资助金额:$8.26万
-
财政年份:1998
-
负责人:YU-WEN HWANG
-
依托单位:
RAS GENES BY DOMINANT NEGATIVE MUTANTS
-
批准号:2095479
-
项目类别:
-
资助金额:$12.32万
-
财政年份:1990
-
负责人:YU-WEN HWANG
-
依托单位:
RAS GENES BY DOMINANT NEGATIVE MUTANTS
-
批准号:3460110
-
项目类别:
-
资助金额:$10.78万
-
财政年份:1990
-
负责人:YU-WEN HWANG
-
依托单位:
RAS GENES BY DOMINANT NEGATIVE MUTANTS
-
批准号:3460112
-
项目类别:
-
资助金额:$10.38万
-
财政年份:1990
-
负责人:YU-WEN HWANG
-
依托单位:
RAS GENES BY DOMINANT NEGATIVE MUTANTS
-
批准号:3460113
-
项目类别:
-
资助金额:$10.96万
-
财政年份:1990
-
负责人:YU-WEN HWANG
-
依托单位:
海外基金