MOLECULAR MECHANISMS OF GUANYLATE CYCLASE ACTIVATION
鸟苷酸环化酶激活的分子机制
基本信息
- 批准号:2898769
- 负责人:
- 金额:$ 4.08万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1997
- 资助国家:美国
- 起止时间:1997-07-01 至 2001-06-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION: (Adapted from the Applicant's Abstract) This is a revised
proposal to investigate the involvement of a protein called the guanylate
cyclase regulatory protein (GCRP) in the regulation of ANF-stimulated
guanylate cyclase activity. This protein which was recently cloned and
expressed in the applicant's laboratory has been shown to amplify
ANF-dependent cyclase activity in cotransfection experiments. The applicant
hypothesizes that; (1) guanylate cyclase exists in an active and inactive
form and that the presence of ANF and ATP promotes the development of the
former; (2) the inactive form is suppressed by an autoinhibitory site
present in the kinase-like domain of the cyclase and (3) in the presence of
ANF and ATP, GCRP, and/or its splice variant GCRP-2, associates with the
cyclase and induces a conformational change which releases the inhibitory
constraint imposed on the active site. To evaluate this hypothesis the
applicant proposes to: (1) locate the autoinhibitory site on the guanylate
cyclase molecule using site-directed mutagenesis and to determine whether
ANF and ATP activate the cyclase by releasing the inhibitory constraint, (2)
investigate whether ANF induces the association of GCRP and GCRP-2 with
guanylate cyclase and (3) examine whether limited proteolysis or binding at
the autoinhibitory site induces a conformational change at the active site
of the cyclase.
描述:(改编自申请人的摘要)这是一份修订后的
关于调查一种名为鸟苷的蛋白质参与的建议
环化调节蛋白(GCRP)对心钠素刺激的调节作用
鸟苷环化酶活力。这种最近被克隆的蛋白质
在申请人的实验室中的表达已经被证明放大了
共转染实验中ANF依赖的环化酶活性。申请人
假设:(1)鸟苷环化酶以活性和非活性形式存在
形式,ANF和ATP的存在促进了
前者;(2)非活性形式被自身抑制部位抑制
存在于环化酶的激酶样结构域中,以及(3)在存在
ANF和ATP、GCRP和/或其剪接变异体GCRP-2与
环化酶并诱导构象变化,从而释放抑制作用
对活动站点施加的限制。为了评估这一假设,
申请人建议:(1)在鸟粪上定位自身抑制部位
利用定点突变技术检测环化酶分子
心钠素和三磷酸腺苷通过释放抑制约束激活环化酶,(2)
研究ANF是否诱导GCRP和GCRP-2与
鸟苷环化酶和(3)检测有限的蛋白分解或结合在
自抑制部位在活性部位引起构象变化
是循环酶的。
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('CHUNG-HO CHANG', 18)}}的其他基金
Interactions of ANG II AT2 receptor signaling with ANF
ANG II AT2 受体信号传导与 ANF 的相互作用
- 批准号:
6589305 - 财政年份:2002
- 资助金额:
$ 4.08万 - 项目类别:
Interactions of ANG II AT2 receptor signaling with ANF
ANG II AT2 受体信号传导与 ANF 的相互作用
- 批准号:
6458452 - 财政年份:2001
- 资助金额:
$ 4.08万 - 项目类别:
MOLECULAR MECHANISMS OF GUANYLATE CYCLASE ACTIVATION
鸟苷酸环化酶激活的分子机制
- 批准号:
2030209 - 财政年份:1997
- 资助金额:
$ 4.08万 - 项目类别:
MOLECULAR MECHANISMS OF GUANYLATE CYCLASE ACTIVATION
鸟苷酸环化酶激活的分子机制
- 批准号:
6030766 - 财政年份:1997
- 资助金额:
$ 4.08万 - 项目类别:
MOLECULAR MECHANISMS OF GUANYLATE CYCLASE ACTIVATION
鸟苷酸环化酶激活的分子机制
- 批准号:
6436131 - 财政年份:1997
- 资助金额:
$ 4.08万 - 项目类别:
MOLECULAR MECHANISMS OF GUANYLATE CYCLASE ACTIVATION
鸟苷酸环化酶激活的分子机制
- 批准号:
2735337 - 财政年份:1997
- 资助金额:
$ 4.08万 - 项目类别:
MOLECULAR MECHANISMS OF GUANYLATE CYCLASE ACTIVATION
鸟苷酸环化酶激活的分子机制
- 批准号:
6183755 - 财政年份:1997
- 资助金额:
$ 4.08万 - 项目类别:
Interactions of ANG II AT2 receptor signaling with ANF
ANG II AT2 受体信号传导与 ANF 的相互作用
- 批准号:
6326314 - 财政年份:1989
- 资助金额:
$ 4.08万 - 项目类别:
ATP-MEDIATED GUANYLATE CYCLASE ACTIVATION IN RAT LUNG MEMBRANES
大鼠肺膜中 ATP 介导的鸟苷酸环化酶激活
- 批准号:
3889993 - 财政年份:
- 资助金额:
$ 4.08万 - 项目类别:
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