REGULATION OF GLUCOCORTICOID RECEPTOR FUNCTION BY CAMP
CAMP 对糖皮质激素受体功能的调节
基本信息
- 批准号:3237344
- 负责人:
- 金额:$ 14.25万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1987
- 资助国家:美国
- 起止时间:1987-01-01 至 1989-12-31
- 项目状态:已结题
- 来源:
- 关键词:T lymphocyte cell fusion cyclic AMP density gradient ultracentrifugation dexamethasone drug resistance gel electrophoresis gene expression genetic manipulation glucocorticoids hormone regulation /control mechanism leukocyte activation /transformation lymphoma messenger RNA phosphorylation protein kinase tissue /cell culture
项目摘要
The overall goal is to achieve a greater understanding of the
mechanisms by which glucocorticoid hormones and hormones which act
through cAMP regulate lymphoid viability and growth. Both steroids
and cyclic nucleotide have the demonstrated capacity to suppress
the immune system as a part of an organism's response to stress.
The primary transducers for these agents are known to be a gene-
regulating receptor and a protein kinase, but the immediate
functions that they affect are only partially understood. Evidence
of crossregulation is presented, showing that cAMP has the ability
to promote an increase of glucocorticoid binding capacity in a
murine lymphoma line, WEHI-7. Two possible mechanisms are
proposed: 1) Conversion of a cryptic pool of receptors into an
active form; 2) Increased synthesis of receptor protein. The
involvement of receptor modification vs. synthesis will be studied
using 2D-gel electrophoresis, thioredoxin assays, density gradient
analysis and molecular probes for synthesis of receptor protein and
messenger RNA.
At certain stages of T-cell differentiation, glucocorticoids and
cyclic nucleotide can elicit a cytolytic response. This behavior
has provided a basis for the use of steroids in treatment of
certain forms of leukemia. The cytolytic response has also
presented a tool for selection of resistant variants containing
altered glucocorticoid receptors and cyclic AMP-dependent protein
kinase. This proposal deals with the discovery and
characterization of a "second generation" of steroid/cyclic
nucleotide resistant variants. It was found that ac initial
selection for resistance to cAMP in the murine lymphoma WEHI-7 acts
as a permissive step towards selection of steroid resistance at s
high frequency. The results indicate that the variants which have
been obtained represent new forms of steroid resistance, possibly
involving functions that activate the glucocorticoid receptor into
a steroid binding state. Characterization of these variant cell
lines is proposed in an attempt to identify the altered functions
which lead to the loss of functional receptor.
总体目标是加深对
糖皮质激素及其作用机制
通过 cAMP 调节淋巴活力和生长。 两种类固醇
和环核苷酸具有抑制的能力
免疫系统是有机体对压力做出反应的一部分。
已知这些药物的主要传感器是基因
调节受体和蛋白激酶,但直接
它们所影响的功能仅被部分了解。 证据
提出了交叉调节,表明 cAMP 具有
促进糖皮质激素结合能力的增加
鼠淋巴瘤系,WEHI-7。 两种可能的机制是
建议:1)将一个神秘的受体池转化为一个
主动形式; 2) 受体蛋白的合成增加。 这
将研究受体修饰与合成的参与
使用 2D 凝胶电泳、硫氧还蛋白测定、密度梯度
受体蛋白合成的分析和分子探针
信使RNA。
在 T 细胞分化的某些阶段,糖皮质激素和
环核苷酸可引发溶细胞反应。 这种行为
为类固醇的治疗提供了基础
某些形式的白血病。 细胞溶解反应也
提出了一种选择耐药变体的工具,其中包含
改变糖皮质激素受体和环AMP依赖性蛋白
激酶。 该提案涉及发现和
“第二代”类固醇/环状化合物的表征
核苷酸抗性变体。 发现ac初始
小鼠淋巴瘤 WEHI-7 中 cAMP 抗性的选择
作为选择类固醇抗性的允许步骤
高频。 结果表明,具有
所获得的代表类固醇抗性的新形式,可能
涉及激活糖皮质激素受体的功能
类固醇结合状态。 这些变异细胞的表征
提出线路是为了尝试识别改变的功能
从而导致功能性受体的丧失。
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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{{ truncateString('DONALD J GRUOL', 18)}}的其他基金
REGULATION OF GLUCOCORTICOID RECEPTOR FUNCTION BY CAMP
CAMP 对糖皮质激素受体功能的调节
- 批准号:
3237349 - 财政年份:1987
- 资助金额:
$ 14.25万 - 项目类别:
REGULATION OF GLUCOCORTICOID RECEPTOR FUNCTION BY CAMP
CAMP 对糖皮质激素受体功能的调节
- 批准号:
3237350 - 财政年份:1987
- 资助金额:
$ 14.25万 - 项目类别:
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