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REGULATION OF GLUCOCORTICOID RECEPTOR FUNCTION BY CAMP

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
负责人:
DONALD J GRUOL
金额:
$14.19万
依托单位国家:
美国
项目类别:
财政年份:
1987
资助国家:
美国
项目状态:
已结题
起止时间:
1987-01-01 至 1991-03-31

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中文摘要
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英文摘要
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.
期刊论文(5)
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科研奖励(0)
会议论文
Transformed glucocorticoid receptors consist of multiple subspecies with differing capacities to bind DNA-cellulose.
转化的糖皮质激素受体由具有不同 DNA-纤维素结合能力的多个亚种组成。
DOI: 10.1021/bi00433a028
发表时间: 1989
期刊: Biochemistry
影响因子: 2.9
作者: [Gruol,DJ, Wolfe,KA]
通讯作者: Wolfe,KA
High-resolution anion exchange chromatography of the glucocorticoid receptor from WEHI-7 cells.
WEHI-7 细胞糖皮质激素受体的高分辨率阴离子交换色谱。
DOI: 10.1016/0022-4731(88)90108-2
发表时间: 1988
期刊: Journal of steroid biochemistry
影响因子: --
作者: [Gruol,DJ, Campbell,NF, Bourgeois,S]
通讯作者: Bourgeois,S
Analysis of glucocorticoid receptor subspecies binding to DNA-cellulose and isolated nuclei.
糖皮质激素受体亚种与 DNA-纤维素和分离细胞核结合的分析。
DOI: 10.1016/0022-4731(89)90101-5
发表时间: 1989
期刊: Journal of steroid biochemistry
影响因子: --
作者: [Gruol,DJ, Wolfe,KA, Safarian,S]
通讯作者: Safarian,S
Transformation of glucocorticoid receptors bound to the antagonist RU 486: effects of alkaline phosphatase.
与拮抗剂 RU 486 结合的糖皮质激素受体的转化:碱性磷酸酶的作用。
DOI: 10.1021/bi00486a026
发表时间: 1990
期刊: Biochemistry
影响因子: 2.9
作者: [Gruol,DJ, Wolfe,KA]
通讯作者: Wolfe,KA
STEROID INTERACTIONS WITH P GLYCOPROTEINS
  • 批准号:
    2634290
  • 项目类别:
  • 资助金额:
    $23.6万
  • 财政年份:
    1997
  • 负责人:
    DONALD J GRUOL
  • 依托单位:
STEROID INTERACTIONS WITH P GLYCOPROTEINS
  • 批准号:
    2540295
  • 项目类别:
  • 资助金额:
    $22.91万
  • 财政年份:
    1997
  • 负责人:
    DONALD J GRUOL
  • 依托单位:
STEROID INTERACTIONS WITH P GLYCOPROTEINS
  • 批准号:
    2856791
  • 项目类别:
  • 资助金额:
    $24.3万
  • 财政年份:
    1997
  • 负责人:
    DONALD J GRUOL
  • 依托单位:
REGULATION OF GLUCOCORTICOID RECEPTOR FUNCTION BY CAMP
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