Molecular Dissection of IGF2R Growth Suppressor Activity

IGF2R 生长抑制活性的分子剖析

基本信息

项目摘要

DESCRIPTION (provided by applicant): Through its many ligand-binding functions, the insulin-like growth factor Il/mannose 6-phosphate receptor (IGF2R) is responsible for transporting mannose-6-phosphate (Man-6-P)-bearing lysosomal enzymes to their appropriate intracellular destination, for mediating uptake and subsequent degradation of the mitogen, insulin-like growth factor 11 (IGF-II), and for facilitating activation of the growth inhibitor, transforming growth factor-b (TGF-b). Each of these activities is consistent with the proposed role of the IGF2R as a tumor suppressor, yet the question of which ligand-binding functions of the IGF2R are responsible for the cell-growth suppressor activity have not been directly addressed. This project will test the hypothesis that the IGF2R's growth suppressor activity depends on the efficient operation of both its IGF-II and Man-6-F binding functions, by the following specific aims: 1) To measure the growth-suppressive effects of wild-type IGF2R vs. receptors mutated in the Man-6-P vs. IGF-II binding functions. IGF2R-deficient cell lines transfected with wild-type IGF2R cDNA expression constructs or IGF2R mutants defective in binding IGF-II or Man-6-P ligands will be analyzed for proliferation relative to vector-transfected controls. Our expectation is that increased wild-type IGF2R expression will inhibit cell growth, and that the mutants will show impairment of this growth-suppressive activity. 2) To determine the effects of cancer-associated M6P/IGF2R missense or truncation mutations on the growth-suppressive activity of the IGF2R. We expect that missense mutations will exhibit reductions in IGF2R function and that truncation mutants may have novel dominant-negative effects. 3) To assess the contribution to the receptor's growth-suppressive activity of pre- and post-receptor binding events that depend on IGF2R dimerization, i.e. development of high-affinity ligand binding and enhanced internalization. These studies will contribute to understanding the receptor's tumor suppressor function and permit rational design of strategies that exploit the IGF2R in cancer prevention and therapy.
说明书(由申请人提供):通过其许多配体结合功能, 胰岛素样生长因子Il/甘露糖6-磷酸受体(IGF2R)是 负责转运含甘露糖-6-磷酸(Man-6-P)的溶酶体 酶到其适当的细胞内目的地,用于中介摄取 以及随后有丝分裂原胰岛素样生长因子11的降解 (IGF-II),并促进生长抑制因子的激活,转化 生长因子-b(TGF-b)。这些活动中的每一个都与 IGF2R作为肿瘤抑制因子的建议作用,但问题是 IGF2R的配体结合功能对细胞生长起作用 抑制者的活动尚未得到直接解决。该项目将测试 假设IGF2R的生长抑制活性依赖于 其IGF-II和Man-6-F结合功能的有效运行,通过 具体目标如下:1)衡量以下因素对增长的抑制作用 野生型IGF2R与受体在Man-6-P与IGF-II结合中的突变 功能。野生型IGF2R基因导入的IGF2R缺陷细胞系 IGF-II或Man-6-P结合缺陷的表达载体或IGF2R突变体 将分析与载体转染相关的配体的增殖情况。 控制。我们的预期是,野生型IGF2R表达增加将 抑制细胞生长,而突变体将表现出这种损伤 抑制生长的活动。2)确定癌症相关疾病的影响 M6P/IGF2R错义或截短突变对生长抑制活性的影响 IGF2R。我们预计错义突变将在 IGF2R功能和截断突变体可能具有新的显性-负性 效果。3)评估受体对生长抑制的作用 依赖IGF2R的受体前和受体后结合事件的活性 二聚化,即发展高亲和力的配体结合和增强 内部化。这些研究将有助于了解受体的 肿瘤抑制功能,并允许合理设计利用 IGF2R在肿瘤防治中的应用

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 }}

RICHARD G. MACDONALD其他文献

RICHARD G. MACDONALD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('RICHARD G. MACDONALD', 18)}}的其他基金

IGF-II-Based Approach to Therapy for Pancreatic Cancer
基于 IGF-II 的胰腺癌治疗方法
  • 批准号:
    9110216
  • 财政年份:
    2015
  • 资助金额:
    $ 16.54万
  • 项目类别:
Molecular Dissection of IGF2R Growth Suppressor Activity
IGF2R 生长抑制活性的分子剖析
  • 批准号:
    6515149
  • 财政年份:
    2001
  • 资助金额:
    $ 16.54万
  • 项目类别:
Molecular Dissection of IGF2R Growth Suppressor Activity
IGF2R 生长抑制活性的分子剖析
  • 批准号:
    6359218
  • 财政年份:
    2001
  • 资助金额:
    $ 16.54万
  • 项目类别:
Molecular Dissection of IGF2R Growth Suppressor Activity
IGF2R 生长抑制活性的分子剖析
  • 批准号:
    6767546
  • 财政年份:
    2001
  • 资助金额:
    $ 16.54万
  • 项目类别:
MAPPING THE IGF II BINDING SITE OF THE IGF II RECEPTOR
绘制 IGF II 受体的 IGF II 结合位点图谱
  • 批准号:
    2143619
  • 财政年份:
    1996
  • 资助金额:
    $ 16.54万
  • 项目类别:
MAPPING THE IGF-II BINDING SITE OF THE IGF-II RECEPTOR
绘制 IGF-II 受体的 IGF-II 结合位点图谱
  • 批准号:
    2143617
  • 财政年份:
    1995
  • 资助金额:
    $ 16.54万
  • 项目类别:
MAPPING THE IGF-II BINDING SITE OF THE IGF-II RECEPTOR
绘制 IGF-II 受体的 IGF-II 结合位点图谱
  • 批准号:
    2143616
  • 财政年份:
    1994
  • 资助金额:
    $ 16.54万
  • 项目类别:
MAPPING THE IGF-II BINDING SITE OF THE IGF-II RECEPTOR
绘制 IGF-II 受体的 IGF-II 结合位点图谱
  • 批准号:
    2143615
  • 财政年份:
    1994
  • 资助金额:
    $ 16.54万
  • 项目类别:
MAPPING THE IGF-II BINDING SITE OF THE IGF-II RECEPTOR
绘制 IGF-II 受体的 IGF-II 结合位点图谱
  • 批准号:
    2143618
  • 财政年份:
    1994
  • 资助金额:
    $ 16.54万
  • 项目类别:
BIOSYNTHESIS AND PROCESSING OF THE IGF-II RECEPTOR
IGF-II 受体的生物合成和加工
  • 批准号:
    3446013
  • 财政年份:
    1984
  • 资助金额:
    $ 16.54万
  • 项目类别:

相似海外基金

Bridging the Gap: Next-Gen Tools for Accurate Prediction of Disordered Protein Binding Sites
弥合差距:准确预测无序蛋白质结合位点的下一代工具
  • 批准号:
    24K15172
  • 财政年份:
    2024
  • 资助金额:
    $ 16.54万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Design of protein crystal templates with multiple binding sites for tracking metal complex reactions.
设计具有多个结合位点的蛋白质晶体模板,用于跟踪金属络合物反应。
  • 批准号:
    23K04928
  • 财政年份:
    2023
  • 资助金额:
    $ 16.54万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Dynamic changes in PIP2 binding sites and their impact on axonal targeting and function of epilepsy-associated KCNQ/Kv7 channels
PIP2 结合位点的动态变化及其对癫痫相关 KCNQ/Kv7 通道的轴突靶向和功能的影响
  • 批准号:
    10744934
  • 财政年份:
    2023
  • 资助金额:
    $ 16.54万
  • 项目类别:
Computational methods to identify small molecule RNA binding sites
识别小分子 RNA 结合位点的计算方法
  • 批准号:
    573688-2022
  • 财政年份:
    2022
  • 资助金额:
    $ 16.54万
  • 项目类别:
    University Undergraduate Student Research Awards
Identification of potential drug binding sites within allosteric networks in cyclic nucleotide modulated channels
环核苷酸调节通道变构网络内潜在药物结合位点的鉴定
  • 批准号:
    10704557
  • 财政年份:
    2022
  • 资助金额:
    $ 16.54万
  • 项目类别:
Identification of potential drug binding sites within allosteric networks in cyclic nucleotide modulated channels
环核苷酸调节通道变构网络内潜在药物结合位点的鉴定
  • 批准号:
    10537846
  • 财政年份:
    2022
  • 资助金额:
    $ 16.54万
  • 项目类别:
Identifying new types of inhibitors in quinone binding sites in photosynthetic enzymes
鉴定光合酶醌结合位点的新型抑制剂
  • 批准号:
    2753921
  • 财政年份:
    2022
  • 资助金额:
    $ 16.54万
  • 项目类别:
    Studentship
Development of broad nanovaccines targeting diverse coronavirus receptor-binding sites
开发针对不同冠状病毒受体结合位点的广泛纳米疫苗
  • 批准号:
    10328140
  • 财政年份:
    2022
  • 资助金额:
    $ 16.54万
  • 项目类别:
Exploiting Water Network Perturbations in Protein Binding Sites
利用蛋白质结合位点的水网络扰动
  • 批准号:
    10621368
  • 财政年份:
    2021
  • 资助金额:
    $ 16.54万
  • 项目类别:
SBIR Phase I: Nonlinear optical method for identifying protein-ligand binding sites
SBIR 第一阶段:识别蛋白质-配体结合位点的非线性光学方法
  • 批准号:
    2111821
  • 财政年份:
    2021
  • 资助金额:
    $ 16.54万
  • 项目类别:
    Standard Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了