Systematic approaches to reveal novel regulatory functions of tyrosine phosphorylation
揭示酪氨酸磷酸化新调节功能的系统方法
基本信息
- 批准号:10029062
- 负责人:
- 金额:$ 36.01万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-15 至 2025-06-30
- 项目状态:未结题
- 来源:
- 关键词:AddressBiochemicalCell Signaling ProcessCell physiologyCellsCuesDecision MakingDiabetes MellitusDiseaseGrowthHumanIn VitroInflammationLocationMalignant NeoplasmsMediatingOutcomePhenotypePhosphorylationPhysiologicalProteomeRoleSignal TransductionSiteSpecificityStructureTertiary Protein StructureTestingTyrosineTyrosine PhosphorylationWorkbaseextracellularfallsimprovednew therapeutic targetnovel
项目摘要
Project Summary
Many cell signaling networks rely on tyrosine phosphorylation to convert extracellular cues into cell phenotypic
outcomes. Tyrosine phosphorylation (pTyr) is important to diverse cellular processes and is often implicated in
disease. There has been explosive growth in the identification of pTyr, with 46,000 pTyr sites now known to exist
in the human proteome and we understand the function of only a small percentage of these sites. This work fo-
cuses on a uniquely tyrosine phenomenon of phosphorylation – 25% of pTyr fall within protein domains, which are
central to pTyr-mediated signaling networks. We propose to exploit the fact that protein domains are conserved
both structurally and functionally by focusing on tyrosine phosphorylation that is structurally conserved within do-
mains. The fundamental premise is that the functional effect of pTyr within a specific structural location within a
domain will have the same effect across all domains that share it. This project will specifically address the novel
possibility that the specificity of multiple types of domains for their interacting partners is regulated by tyrosine
phosphorylation occurring within the domain. This work is enabled by integrated computational and experimental
approaches, which can: identify conserved tyrosine phosphorylation, hypothesize effects based on the role of
that conserved tyrosine within domain function, use physiological evidence to understand its involvement in cell
signaling processes, and systematically test pTyr effects on domain function in vitro and within cell signaling net-
works. Focusing on two important interaction domains in cell signaling, this work will likely reveal new paradigms
involving pTyr-mediated signaling, which has broad implications in our basic understanding of cell signaling and
could help identify new therapeutic targets across a broad range of diseases.
项目摘要
许多细胞信号网络依赖于酪氨酸磷酸化将细胞外信号转化为细胞表型信号。
结果。酪氨酸磷酸化(pTyr)对于不同的细胞过程是重要的,并且通常涉及
疾病对pTyr的鉴定呈爆炸性增长,目前已知存在46,000个pTyr位点
在人类蛋白质组中,我们只了解这些位点中一小部分的功能。这项工作是为了-
这是一种独特的酪氨酸磷酸化现象,25%的pTyr位于蛋白质结构域内,
pTyr介导的信号网络的中心。我们建议利用蛋白质结构域保守的事实
在结构上和功能上,通过关注在DO中结构保守的酪氨酸磷酸化,
电源。基本前提是,pTyr在特定结构位置内的功能效应,
域将有相同的效果在所有域共享它。这个项目将专门解决小说
多种类型的结构域的相互作用伙伴的特异性受酪氨酸调节的可能性
磷酸化发生在结构域内。这项工作是通过集成的计算和实验
方法,这可以:确定保守的酪氨酸磷酸化,假设的作用基础上的作用,
保守酪氨酸结构域功能,使用生理学证据来了解其参与细胞
信号转导过程,并系统地测试pTyr对体外和细胞信号转导网络内结构域功能的影响,
工程.聚焦于细胞信号传导中的两个重要的相互作用域,这项工作将可能揭示新的范式
涉及pTyr介导的信号传导,这在我们对细胞信号传导的基本理解中具有广泛的意义,
可以帮助确定广泛疾病的新治疗靶点。
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 }}
Kristen M Naegle其他文献
Kristen M Naegle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('Kristen M Naegle', 18)}}的其他基金
Protein Phosphorylation Networks in Health and Disease
健康和疾病中的蛋白质磷酸化网络
- 批准号:
10682983 - 财政年份:2023
- 资助金额:
$ 36.01万 - 项目类别:
Inferring Kinase Activity from Tumor Phosphoproteomic Data
从肿瘤磷酸化蛋白质组数据推断激酶活性
- 批准号:
10743051 - 财政年份:2023
- 资助金额:
$ 36.01万 - 项目类别:
A synthetic toolkit for the recombinant production of tyrosine phosphorylated proteins and peptides
用于重组生产酪氨酸磷酸化蛋白和肽的合成工具包
- 批准号:
10673930 - 财政年份:2022
- 资助金额:
$ 36.01万 - 项目类别:
Systematic approaches to reveal novel regulatory functions of tyrosine phosphorylation
揭示酪氨酸磷酸化新调节功能的系统方法
- 批准号:
10456652 - 财政年份:2020
- 资助金额:
$ 36.01万 - 项目类别:
Systematic approaches to reveal novel regulatory functions of tyrosine phosphorylation
揭示酪氨酸磷酸化新调节功能的系统方法
- 批准号:
10256636 - 财政年份:2020
- 资助金额:
$ 36.01万 - 项目类别:
Systematic approaches to reveal novel regulatory functions of tyrosine phosphorylation
揭示酪氨酸磷酸化新调节功能的系统方法
- 批准号:
10657453 - 财政年份:2020
- 资助金额:
$ 36.01万 - 项目类别:
Inferring Kinase Activity Profiles from Phosphoproteomic Data
从磷酸化蛋白质组数据推断激酶活性概况
- 批准号:
9755392 - 财政年份:2018
- 资助金额:
$ 36.01万 - 项目类别:
相似海外基金
CAREER: Biochemical and Structural Mechanisms Controlling tRNA-Modifying Metalloenzymes
职业:控制 tRNA 修饰金属酶的生化和结构机制
- 批准号:
2339759 - 财政年份:2024
- 资助金额:
$ 36.01万 - 项目类别:
Continuing Grant
Systematic manipulation of tau protein aggregation: bridging biochemical and pathological properties
tau 蛋白聚集的系统操作:桥接生化和病理特性
- 批准号:
479334 - 财政年份:2023
- 资助金额:
$ 36.01万 - 项目类别:
Operating Grants
Diurnal environmental adaptation via circadian transcriptional control based on a biochemical oscillator
基于生化振荡器的昼夜节律转录控制的昼夜环境适应
- 批准号:
23H02481 - 财政年份:2023
- 资助金额:
$ 36.01万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Leveraging releasable aryl diazonium ions to probe biochemical systems
利用可释放的芳基重氮离子探测生化系统
- 批准号:
2320160 - 财政年份:2023
- 资助金额:
$ 36.01万 - 项目类别:
Standard Grant
Biochemical Mechanisms for Sustained Humoral Immunity
持续体液免疫的生化机制
- 批准号:
10637251 - 财政年份:2023
- 资助金额:
$ 36.01万 - 项目类别:
Structural and biochemical investigations into the mechanism and evolution of soluble guanylate cyclase regulation
可溶性鸟苷酸环化酶调节机制和进化的结构和生化研究
- 批准号:
10604822 - 财政年份:2023
- 资助金额:
$ 36.01万 - 项目类别:
Enhanced Biochemical Monitoring for Aortic Aneurysm Disease
加强主动脉瘤疾病的生化监测
- 批准号:
10716621 - 财政年份:2023
- 资助金额:
$ 36.01万 - 项目类别:
Converting cytoskeletal forces into biochemical signals
将细胞骨架力转化为生化信号
- 批准号:
10655891 - 财政年份:2023
- 资助金额:
$ 36.01万 - 项目类别:
Chemical strategies to investigate biochemical crosstalk in human chromatin
研究人类染色质生化串扰的化学策略
- 批准号:
10621634 - 财政年份:2023
- 资助金额:
$ 36.01万 - 项目类别:
Examination of risk assessment and biochemical assessment of fracture development focusing on the body composition of patients with rheumatoid arthritis
关注类风湿性关节炎患者身体成分的骨折发生风险评估和生化评估检查
- 批准号:
22KJ2600 - 财政年份:2023
- 资助金额:
$ 36.01万 - 项目类别:
Grant-in-Aid for JSPS Fellows