MOLECULAR MECHANISMS OF GUANYLATE CYCLASE ACTIVATION
MOLECULAR MECHANISMS OF GUANYLATE CYCLASE ACTIVATION
批准号:
2898769
负责人:
CHUNG-HO CHANG
金额:
$4.08万
依托单位国家:
美国
项目类别:
财政年份:
1997
资助国家:
美国
项目状态:
已结题
起止时间:
1997-07-01 至 2001-06-30
中文摘要
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
使用定点突变环化酶分子并确定是否
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。
英文摘要
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.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Interactions of ANG II AT2 receptor signaling with ANF
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批准号:6589305
-
项目类别:
-
资助金额:$25.95万
-
财政年份:2002
-
负责人:CHUNG-HO CHANG
-
依托单位:
Interactions of ANG II AT2 receptor signaling with ANF
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批准号:6458452
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项目类别:
-
资助金额:$25.95万
-
财政年份:2001
-
负责人:CHUNG-HO CHANG
-
依托单位:
IDENTIFICATION OF FREE RADICAL RESISTANT GENES
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批准号:2409880
-
项目类别:
-
资助金额:$7.65万
-
财政年份:1997
-
负责人:CHUNG-HO CHANG
-
依托单位:
MOLECULAR MECHANISMS OF GUANYLATE CYCLASE ACTIVATION
-
批准号:2030209
-
项目类别:
-
资助金额:$14.99万
-
财政年份:1997
-
负责人:CHUNG-HO CHANG
-
依托单位:
MOLECULAR MECHANISMS OF GUANYLATE CYCLASE ACTIVATION
-
批准号:6030766
-
项目类别:
-
资助金额:$22.94万
-
财政年份:1997
-
负责人:CHUNG-HO CHANG
-
依托单位:
MOLECULAR MECHANISMS OF GUANYLATE CYCLASE ACTIVATION
-
批准号:6436131
-
项目类别:
-
资助金额:$4.49万
-
财政年份:1997
-
负责人:CHUNG-HO CHANG
-
依托单位:
MOLECULAR MECHANISMS OF GUANYLATE CYCLASE ACTIVATION
-
批准号:2735337
-
项目类别:
-
资助金额:$15.44万
-
财政年份:1997
-
负责人:CHUNG-HO CHANG
-
依托单位:
MOLECULAR MECHANISMS OF GUANYLATE CYCLASE ACTIVATION
-
批准号:6183755
-
项目类别:
-
资助金额:$19.31万
-
财政年份:1997
-
负责人:CHUNG-HO CHANG
-
依托单位:
Interactions of ANG II AT2 receptor signaling with ANF
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批准号:6326314
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项目类别:
-
资助金额:$25.95万
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财政年份:1989
-
负责人:CHUNG-HO CHANG
-
依托单位:
ATP-MEDIATED GUANYLATE CYCLASE ACTIVATION IN RAT LUNG MEMBRANES
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批准号:3889993
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项目类别:
-
资助金额:$0.0万
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财政年份:--
-
负责人:CHUNG-HO CHANG
-
依托单位:
海外基金