HUMAN CELL SURFACE ANTIGENS--TRANSFERRIN RECEPTORS
人类细胞表面抗原--转铁蛋白受体
基本信息
- 批准号:3172612
- 负责人:
- 金额:$ 25.57万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1983
- 资助国家:美国
- 起止时间:1983-06-01 至 1996-05-31
- 项目状态:已结题
- 来源:
- 关键词:biological products cell growth regulation chemical binding chimeric proteins endocytosis genetic library genetic manipulation human genetic material tag immunochemistry laboratory mouse membrane fusion molecular site monoclonal antibody protein structure function protein transport receptor expression recombinant proteins tissue /cell culture transfection transferrin transferrin receptor
项目摘要
The long-term goal of this project is to understand the structure-function
relationship of the transferrin receptor and its role in cell growth. The
proposed work will contribute to our appreciation of the molecular basis of
receptor-mediated endocytosis and recycling. It will also contribute to
the evaluation of the transferrin receptor as a potential target for
immunotherapy in the treatment of cancer and the development of more
effective methods of antibody-mediated cell-specific drug targeting. The
specific aims are: 1) to characterize the external domain of the human
transferrin receptor immunochemically and map the transferrin binding site
by structural analysis of chick-human hybrid receptors; 2) to determine
whether the YXRF internalization signal found in the amino-terminal
cytoplasmic domain of the human transferrin receptor is sufficient to
induce rapid endocytosis of other Type II membrane proteins; 3) to express
and isolate sufficient soluble human transferrin receptor external and
cytoplasmic domains for biophysical characterization; 4) to characterize
the interaction of the transferrin receptor cytoplasmic domain with
structural components of coated pits; 5) to investigate the role of the
human transferrin receptor cytoplasmic domain in endosome-endosome fusions;
and 6) to characterize the intracellular compartments through which the
transferrin receptor traffics during endocytosis and recycling.
To achieve these goals, we will use a broad range of experimental methods
derived from molecular biology, protein biochemistry, cell biology, and
immunology. Specifically, we will exploit: 1) the availability of cDNAs
for the human mouse and chicken transferrin receptors; 2) a retroviral
expression system for expressing mutant human transferrin receptors in
chick embryo fibroblasts and analysis of their biological activity; 3)
high-yield protein expression systems in bacteria. Chinese hamster ovary
cells and vaculovirus-infected insect cells that have allowed the
expression of the intact transferrin receptor, and independently, the
cytoplasmic and external domains as soluble recombinant proteins; 4) and
more than 30 monoclonal antibodies against both the external and
cytoplasmic domains of the human transferrin receptor. A major new aspect
of the work is to develop the materials and methods necessary to determine
the 3-dimensional structure of both the cytoplasmic and external domains of
the human transferrin receptor. The former studies will test the validity
of the model we have recently proposed that a Type I turn is the structural
recognition motif for high-efficiency endocytosis.
本项目的长期目标是了解结构-功能
转铁蛋白受体的关系及其在细胞生长中的作用。 的
拟议的工作将有助于我们了解的分子基础,
受体介导的内吞作用和再循环。 它还将协助
转铁蛋白受体作为潜在靶点的评价
免疫疗法在治疗癌症和发展更多
抗体介导的细胞特异性药物靶向的有效方法。 的
具体目标是:1)描述人类的外部领域
转铁蛋白受体的免疫化学和地图转铁蛋白结合位点
通过鸡-人杂交受体的结构分析; 2)确定
在氨基末端发现的YXRF内化信号
人转铁蛋白受体的胞质结构域足以
诱导其他II型膜蛋白快速内吞; 3)表达
并分离足够的可溶性人转铁蛋白受体,
用于生物物理表征的胞质结构域; 4)表征
转铁蛋白受体胞质结构域与
涂层坑的结构成分; 5)调查的作用,
内体-内体融合中人转铁蛋白受体胞质结构域;
和6)表征细胞内区室,
转铁蛋白受体在内吞作用和再循环期间运输。
为了实现这些目标,我们将使用广泛的实验方法
衍生自分子生物学、蛋白质生物化学、细胞生物学,
免疫学 具体来说,我们将利用:1)cDNA的可用性
人、小鼠和鸡转铁蛋白受体; 2)逆转录病毒
用于表达突变型人转铁蛋白受体的表达系统
鸡胚成纤维细胞及其生物学活性分析; 3)
细菌中的高产蛋白表达系统。 中国仓鼠卵巢
细胞和空泡病毒感染的昆虫细胞,
完整转铁蛋白受体的表达,并且独立地,
作为可溶性重组蛋白的胞质和外部结构域; 4)和
超过30种单克隆抗体,
人转铁蛋白受体的胞质结构域。 一个主要的新方面
的工作是开发必要的材料和方法,以确定
细胞质和外部结构域的三维结构
人类转铁蛋白受体 以往的研究将检验其有效性
我们最近提出的模型,即I型转弯是结构性的
高效内吞作用的识别基序。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
IAN S TROWBRIDGE其他文献
IAN S TROWBRIDGE的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('IAN S TROWBRIDGE', 18)}}的其他基金
ANTITUMOR THERAPY WIH ANTITRANSFERRIN RECEPTOR MONOCLONAL ANTIBODIES
使用抗转铁蛋白受体单克隆抗体的抗肿瘤治疗
- 批准号:
6102191 - 财政年份:1997
- 资助金额:
$ 25.57万 - 项目类别:
相似海外基金
A novel mechanism of cell growth regulation by the intrinsically disordered protein, NPM1
内在无序蛋白 NPM1 调节细胞生长的新机制
- 批准号:
26440021 - 财政年份:2014
- 资助金额:
$ 25.57万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Study on the mechanism of cell growth regulation by ST2 and its possible anti-cancerous effect.
ST2调节细胞生长的机制及其可能的抗癌作用研究。
- 批准号:
25460393 - 财政年份:2013
- 资助金额:
$ 25.57万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Molecular Mechanisms for cell growth regulation by Mnk-mediated translational control
Mnk 介导的翻译控制调节细胞生长的分子机制
- 批准号:
24590105 - 财政年份:2012
- 资助金额:
$ 25.57万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Integrating Phosphatidylcholine Metabolism with Cell Growth Regulation
将磷脂酰胆碱代谢与细胞生长调节相结合
- 批准号:
221878 - 财政年份:2010
- 资助金额:
$ 25.57万 - 项目类别:
Operating Grants
UNDERSTANDING THE ROLES OF SMALL GTPASES IN CELL GROWTH REGULATION
了解小 GTP 酶在细胞生长调节中的作用
- 批准号:
7955176 - 财政年份:2009
- 资助金额:
$ 25.57万 - 项目类别:
Roles of the Golgi apparatus in cell growth regulation
高尔基体在细胞生长调节中的作用
- 批准号:
18570173 - 财政年份:2006
- 资助金额:
$ 25.57万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Mechanism of cell growth regulation by small G proteins
小G蛋白调节细胞生长的机制
- 批准号:
17014061 - 财政年份:2005
- 资助金额:
$ 25.57万 - 项目类别:
Grant-in-Aid for Scientific Research on Priority Areas
The role of Kaiso in cell growth regulation
Kaiso 在细胞生长调节中的作用
- 批准号:
302718-2004 - 财政年份:2004
- 资助金额:
$ 25.57万 - 项目类别:
Postgraduate Scholarships - Master's
Bone Cell Growth Regulation by Runx2/Cbfa1
Runx2/Cbfa1 调节骨细胞生长
- 批准号:
6619987 - 财政年份:2003
- 资助金额:
$ 25.57万 - 项目类别:
Bone Cell Growth Regulation by Runx2/Cbfa1
Runx2/Cbfa1 调节骨细胞生长
- 批准号:
6898940 - 财政年份:2003
- 资助金额:
$ 25.57万 - 项目类别: