Regulation of Chemotactic Signaling
趋化信号的调节
基本信息
- 批准号:10386438
- 负责人:
- 金额:$ 12.62万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-06-01 至 2024-03-31
- 项目状态:已结题
- 来源:
- 关键词:Animal ModelArthritisAsthmaAtherosclerosisBehaviorBiochemicalCell LineCell NucleusCell membraneCellsCellular StructuresChemicalsChemotaxisDetectionDiseaseEmbryonic DevelopmentFluorescenceFundingFunding OpportunitiesGTP BindingGoalsHigh Pressure Liquid ChromatographyHumanImmune responseIn VitroKnock-outMalignant NeoplasmsPTEN genePhosphorylationPhysiological ProcessesProto-Oncogene Proteins c-aktRaceRegulationSignal TransductionSystemTherapeutic InterventionX-Ray Crystallographycell motilityextracellularin vivolive cell imagingmigrationparent grantprotein complexprotein protein interactionreconstitutionsingle moleculetherapeutic developmenttumorigenesiswound healing
项目摘要
Summary
Through the funding opportunity described in PAR-20-272, this proposal seeks funds to
purchase a fluorescence-detection HPLC (high-performance liquid chromatography) system to
quantitatively assess stimulation-induced dynamic assembly of protein complexes in
chemotactic signaling. The goals of the parent grant R35GM131768 are to investigate how cells
sense extracellular chemical gradients and control their migration behaviors. First, we will
determine how phosphorylated, GDP-bound RacE activates TORC2 to facilitate AKT
phosphorylation at the leading end of migrating cells while GTP-bound RacE inhibits TORC2 at
the trailing end. This will involve multiple experimental approaches, including cellular
reconstitution using knockout cell lines, biochemical reconstitution of RacE-regulated TORC2
activity with purified proteins, protein interaction analyses at the single-molecule level in vitro,
live imaging of cells, and structural analysis using X-ray crystallography. Second, we will
decipher a key mechanism controlling human PTEN localization at the plasma membrane and
nucleus. Third, we will determine the effects of the manipulation of PTEN localization on
tumorigenesis in vivo using animal models.
总结
通过PAR-20-272所述的供资机会,本提案寻求资金,
购买荧光检测HPLC(高效液相色谱)系统,
定量评估刺激诱导的蛋白质复合物的动态组装,
趋化性信号母基金R35 GM 131768的目标是研究细胞如何
感知细胞外化学梯度并控制其迁移行为。一是
确定磷酸化的GDP结合的RacE如何激活TORC 2以促进AKT
在迁移细胞的前端磷酸化,而GTP结合的RacE抑制TORC 2,
尾端。这将涉及多种实验方法,包括细胞
使用敲除细胞系的重建,RacE调节的TORC 2的生物化学重建
纯化蛋白的活性,体外单分子水平的蛋白相互作用分析,
细胞的活体成像和使用X射线晶体学的结构分析。二是
破译控制人PTEN在质膜定位的关键机制,
原子核第三,我们将确定操作PTEN定位对细胞凋亡的影响。
使用动物模型的体内肿瘤发生。
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)
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Miho Iijima其他文献
Miho Iijima的其他文献
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{{ truncateString('Miho Iijima', 18)}}的其他基金
Mechanism and Function of the Supercomplex KARATE in Insulin Signaling
超级复合物空手道在胰岛素信号传导中的机制和功能
- 批准号:
10444290 - 财政年份:2022
- 资助金额:
$ 12.62万 - 项目类别:
Mechanism and Function of the Supercomplex KARATE in Insulin Signaling
超级复合物空手道在胰岛素信号传导中的机制和功能
- 批准号:
10601093 - 财政年份:2022
- 资助金额:
$ 12.62万 - 项目类别:
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