CARDIAC HYPERTROPHY--ROLE OF NUCLEAR T3 RECEPTORS
CARDIAC HYPERTROPHY--ROLE OF NUCLEAR T3 RECEPTORS
批准号:
3349976
负责人:
EUGENE MORKIN
金额:
$11.73万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1985
资助国家:
美国
项目状态:
已结题
起止时间:
1985-09-30 至 1986-09-29
关键词:
DNA affinity chromatography bacteriophage lambda cell nucleus complementary DNA enzyme linked immunosorbent assay gene expression genetic library genetic manipulation heart enlargement isozymes molecular cloning molecular pathology monoclonal antibody nucleic acid sequence radiotracer triiodothyronine
中文摘要
过量的甲状腺激素导致一种独特的心肌肥厚
以心肌功能增强为特征,这可能与
从低ATPase形式的肌球蛋白转换为高ATPase形式的肌球蛋白
活动。目前,我们实验室正在尝试定义
甲状腺激素调节肌球蛋白同工酶的机制(S)
表情。虽然我们主要关注肌球蛋白的过程
Isoform Switch,我们对缺乏关于
核甲状腺激素结合蛋白本身。因此,
这项拟议研究的主要目的是研究核T3的作用
受体在心肌肥厚的启动和调控中的作用
肌球蛋白同工酶的表达。为了实现这些目标,我们计划,
首先,克隆编码T3受体蛋白的c DNA。
多克隆和单克隆抗体用于鉴定编码该基因的cDNA
在特制的Lambdagt11表达克隆文库中表达蛋白质。
其次,我们建议确定特定的核DNA结合位点
T3受体。我们已经开发了一种分离T3受体的策略
附上其DNA片段,并需要支持才能克隆和
对这些碎片进行排序。这些结果应该会提供重要的新的
与T3受体蛋白及其DNA结构有关的信息
结合部位。这些调查将通过合作进行
在图森的Morkin博士团队和Keith Latham博士的实验室之间
华盛顿健康科学统一服务大学,
D.C.莱瑟姆博士最近研制出了多克隆和单克隆
针对受体蛋白的抗体。我们相信我们组建的团队
可以在阐明甲状腺的机制方面取得重大进展
荷尔蒙对心脏和其他组织的作用。
英文摘要
Excess thyroid hormone induces a unique form of cardiac hypertrophy
characterized by enhanced myocardial performance which may be related to
switching from a low ATPase form of myosin to one with higher ATPase
activity. At present our laboratory is attempting to define the
mechanism(s) by which thyroid hormone regulates myosin isoenzyme
expression. Although we mainly are concerned with the process of myosin
isoform switching, we are impressed with the lack of information about
nuclear thyroid hormone binding proteins themselves. Accordingly, the
major aim of the proposed research is to investigate the role of nuclear T3
receptor in the initiation of cardiac hypertrophy and in the control of
myosin isoenzymes expression. To accomplish these objectives, we plan,
first, to clone the cDNA coding for the T3 receptor protein by using
polyclonal and monoclonal antibodies to identify cDNAs coding for this
protein in a specially constructed Lambdagt11 expression clone bank.
Secondly, we propose to identify specific nuclear DNA binding sites for the
T3 receptor. We have developed a strategy for isolation of the T3 receptor
with its DNA fragment attached and support is requested to clone and
sequence these fragments. These results should provide significant new
information related to the structure of the T3 receptor protein and its DNA
binding sites. These investigations will be carried out by a collaboration
between Dr. Morkin's group in Tucson and Dr. Keith Latham's laboratory at
the Uniformed Services University of the Health Sciences in Washington,
D.C. Dr. Latham recently has developed polyclonal and monoclonal
antibodies to the receptor protein. We believe the team we have assembled
can make significant progress on elucidation of the mechanism of thyroid
hormone actions on the heart and in other tissues.
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会议论文
CORE--STATISTICAL
-
批准号:6109518
-
项目类别:
-
资助金额:$14.32万
-
财政年份:1997
-
负责人:EUGENE MORKIN
-
依托单位:
CONTROL OF CARDIAC MYOSIN HEAVY CHAIN GENES
-
批准号:6109513
-
项目类别:
-
资助金额:$14.32万
-
财政年份:1997
-
负责人:EUGENE MORKIN
-
依托单位:
CELLULAR MECHANISMS IN CARDIAC HYPERTROPHY
-
批准号:3097778
-
项目类别:
-
资助金额:$4.46万
-
财政年份:1989
-
负责人:EUGENE MORKIN
-
依托单位:
CARDIAC HYPERTROPHY--ROLE OF NUCLEAR T3 RECEPTORS
-
批准号:3349978
-
项目类别:
-
资助金额:$11.83万
-
财政年份:1985
-
负责人:EUGENE MORKIN
-
依托单位:
CARDIAC HYPERTROPHY--ROLE OF NUCLEAR T3 RECEPTORS
-
批准号:3349977
-
项目类别:
-
资助金额:$10.27万
-
财政年份:1985
-
负责人:EUGENE MORKIN
-
依托单位:
CELLULAR MECHANISM IN CARDIAC HYPERTROPHY
-
批准号:3097777
-
项目类别:
-
资助金额:$9.94万
-
财政年份:1977
-
负责人:EUGENE MORKIN
-
依托单位:
CELLULAR MECHANISMS IN CARDIAC HYPERTROPHY
-
批准号:3097785
-
项目类别:
-
资助金额:$70.06万
-
财政年份:1977
-
负责人:EUGENE MORKIN
-
依托单位:
CELLULAR MECHANISMS IN CARDIAC HYPERTROPY
-
批准号:2215408
-
项目类别:
-
资助金额:$76.37万
-
财政年份:1977
-
负责人:EUGENE MORKIN
-
依托单位:
CELLULAR MECHANISMS IN CARDIAC HYPERTROPHY
-
批准号:3097784
-
项目类别:
-
资助金额:$64.56万
-
财政年份:1977
-
负责人:EUGENE MORKIN
-
依托单位:
CELLULAR MECHANISMS IN CARDIAC HYPERTROPHY
-
批准号:3097780
-
项目类别:
-
资助金额:$73.31万
-
财政年份:1977
-
负责人:EUGENE MORKIN
-
依托单位:
CELLULAR MECHANISMS IN CARDIAC HYPERTROPHY
-
批准号:3097775
-
项目类别:
-
资助金额:$63.94万
-
财政年份:1977
-
负责人:EUGENE MORKIN
-
依托单位:
CELLULAR MECHANISMS IN CARDIAC HYPERTROPHY
-
批准号:3097782
-
项目类别:
-
资助金额:$66.27万
-
财政年份:1977
-
负责人:EUGENE MORKIN
-
依托单位:
CELLULAR MECHANISMS IN CARDIAC HYPERTROPY
-
批准号:2519263
-
项目类别:
-
资助金额:$85.91万
-
财政年份:1977
-
负责人:EUGENE MORKIN
-
依托单位:
CELLULAR MECHANISMS IN CARDIAC HYPERTROPY
-
批准号:2028015
-
项目类别:
-
资助金额:$79.31万
-
财政年份:1977
-
负责人:EUGENE MORKIN
-
依托单位:
CELLULAR MECHANISMS IN CARDIAC HYPERTROPHY
-
批准号:3097783
-
项目类别:
-
资助金额:$71.73万
-
财政年份:1977
-
负责人:EUGENE MORKIN
-
依托单位:
CELLULAR MECHANISMS IN CARDIAC HYPERTROPY
-
批准号:2215409
-
项目类别:
-
资助金额:$79.43万
-
财政年份:1977
-
负责人:EUGENE MORKIN
-
依托单位:
CELLULAR MECHANISMS IN CARDIAC HYPERTROPHY
-
批准号:3097779
-
项目类别:
-
资助金额:$67.11万
-
财政年份:1977
-
负责人:EUGENE MORKIN
-
依托单位:
CELLULAR MECHANISMS IN CARDIAC HYPERTROPHY
-
批准号:3097781
-
项目类别:
-
资助金额:$82.87万
-
财政年份:1977
-
负责人:EUGENE MORKIN
-
依托单位:
CELLULAR MECHANISMS IN CARDIAC HYPERTROPY
-
批准号:3097776
-
项目类别:
-
资助金额:$73.54万
-
财政年份:1977
-
负责人:EUGENE MORKIN
-
依托单位:
CORE--STATISTICAL
-
批准号:3758114
-
项目类别:
-
资助金额:$0.0万
-
财政年份:--
-
负责人:EUGENE MORKIN
-
依托单位:
海外基金