MAPPING THE IGF-II BINDING SITE OF THE IGF-II RECEPTOR
MAPPING THE IGF-II BINDING SITE OF THE IGF-II RECEPTOR
批准号:
2143615
负责人:
RICHARD G. MACDONALD
金额:
$12.64万
依托单位国家:
美国
项目类别:
财政年份:
1994
资助国家:
美国
项目状态:
已结题
起止时间:
1994-01-01 至 1996-12-31
关键词:
SDS polyacrylamide gel electrophoresis animal genetic material tag chemical binding chimeric proteins complementary DNA crosslink genetic library genetic mapping growth factor receptors high performance liquid chromatography insulinlike growth factor molecular cloning nucleic acid sequence protein sequence protein structure function receptor binding receptor coupling receptor expression site directed mutagenesis tissue /cell culture
中文摘要
胰岛素样生长因子II(IGF-II)受体具有高亲和力
多肽IGF-II与糖基化溶酶体的结合部位
酵素。这种独特的受体在运输溶酶体酶中的关键作用
是公认的,但IGF-II启动信号的机制
IGF-II受体介导的信号转导事件一直存在争议。
为了帮助阐明这一机制,该项目的目标是绘制
两个互补的IGF-II受体ICF-II结合部位的研究
接近了。首先,纯化的125I-IGF-II亲和标记受体将
用内切酶Glu-C消化,然后将多肽区
与IGF-II共价结合的受体将被分离出来进行测序。
第二,编码IGF-II受体的禽类同源基因的cDNA克隆
不结合ICF-II,将通过筛选鸡的cDNA文库来分离
用哺乳动物IGF-II受体cDNA的放射性标记片段。数列
在这些研究中获得的测绘信息和试剂将
用于指定定点突变的靶点
哺乳动物IGF-II受体结合部位及禽类/哺乳类动物的设计
受体嵌合体。野生型、突变型和嵌合型受体将
在哺乳动物细胞中表达,以评估IGF-II结合参数,并
研究IGF-II结合与
信号转导。
英文摘要
The insulin-like growth factor II (IGF-II) receptor has high affinity
binding sites for the polypeptide IGF-II and glycosylated lysosomal
enzymes. This unique receptor's key role in transporting lysosomal enzymes
is well established, but the mechanism by which IGF-II-initiated signal
transduction events are mediated by the IGF-II receptor is controversial.
To help elucidate this mechanism, the objective of this project is to map
the ICF-II binding site of the IGF-II receptor using two complementary
approaches. First, purified 125I-IGF-II affinity-labelled receptors will
be digested with endoproteinase Glu-C, then peptide regions of the
receptor covalently attached to IGF-II will be isolated for sequencing.
Second, cDNA clones encoding the IGF-II receptor's avian homolog, which
does not bind ICF-II, will be isolated by screening chicken cDNA libraries
with radiolabelled fragments of mammalian IGF-II receptor cDNAs. Sequence
and mapping information as well as reagents obtained in those studies will
be used to designate targets for site-directed mutagenesis of the
mammalian receptor's IGF-II binding site and to design avian/mammalian
receptor chimeras. Wild-type, mutant and chimeric receptors will be
expressed in mammalian cells to assess IGF-II binding parameters, and to
investigate structure-function relationships linking IGF-II binding to
signal transduction.
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专著(0)
科研奖励(0)
会议论文
IGF-II-Based Approach to Therapy for Pancreatic Cancer
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批准号:9110216
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项目类别:
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资助金额:$19.57万
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财政年份:2015
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负责人:RICHARD G. MACDONALD
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依托单位:
Molecular Dissection of IGF2R Growth Suppressor Activity
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批准号:6515149
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项目类别:
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资助金额:$16.54万
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财政年份:2001
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负责人:RICHARD G. MACDONALD
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依托单位:
Molecular Dissection of IGF2R Growth Suppressor Activity
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批准号:6634068
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项目类别:
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资助金额:$16.54万
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财政年份:2001
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负责人:RICHARD G. MACDONALD
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依托单位:
Molecular Dissection of IGF2R Growth Suppressor Activity
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批准号:6359218
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项目类别:
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资助金额:$16.25万
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财政年份:2001
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负责人:RICHARD G. MACDONALD
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依托单位:
Molecular Dissection of IGF2R Growth Suppressor Activity
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批准号:6767546
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项目类别:
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资助金额:$16.54万
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财政年份:2001
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负责人:RICHARD G. MACDONALD
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依托单位:
MAPPING THE IGF II BINDING SITE OF THE IGF II RECEPTOR
-
批准号:2143619
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项目类别:
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资助金额:$2.61万
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财政年份:1996
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负责人:RICHARD G. MACDONALD
-
依托单位:
MAPPING THE IGF-II BINDING SITE OF THE IGF-II RECEPTOR
-
批准号:2143617
-
项目类别:
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资助金额:$2.46万
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财政年份:1995
-
负责人:RICHARD G. MACDONALD
-
依托单位:
MAPPING THE IGF-II BINDING SITE OF THE IGF-II RECEPTOR
-
批准号:2143616
-
项目类别:
-
资助金额:$12.51万
-
财政年份:1994
-
负责人:RICHARD G. MACDONALD
-
依托单位:
MAPPING THE IGF-II BINDING SITE OF THE IGF-II RECEPTOR
-
批准号:2143618
-
项目类别:
-
资助金额:$13.07万
-
财政年份:1994
-
负责人:RICHARD G. MACDONALD
-
依托单位:
BIOSYNTHESIS AND PROCESSING OF THE IGF-II RECEPTOR
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批准号:3446013
-
项目类别:
-
资助金额:$5.79万
-
财政年份:1984
-
负责人:RICHARD G. MACDONALD
-
依托单位:
BIOSYNTHESIS AND PROCESSING OF THE IGF-II RECEPTOR
-
批准号:3447273
-
项目类别:
-
资助金额:$6.15万
-
财政年份:1984
-
负责人:RICHARD G. MACDONALD
-
依托单位: