Regulation of Chemotactic Signaling

趋化信号的调节

基本信息

  • 批准号:
    10377388
  • 负责人:
  • 金额:
    $ 40.94万
  • 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

项目摘要

Summary Chemotactic cell migration underlies embryonic development, wound healing and immune responses. Furthermore, aberrant chemotaxis leads to chronic inflammatory disease and tumor metastasis. My laboratory has long been interested in signaling mechanisms that control cell behaviors in chemotaxis. In a chemical gradient, cells polarize intracellular signaling and migrate toward chemoattractants. Ligand binding to chemoattractant receptors selectively activates two kinases, TORC2 and PI3K, at the front of cells. TORC2 and PI3K are the master kinases that induce cytoskeletal remodeling to extend pseudopods and function immediately downstream of chemotactic receptors. Polarized activation of these two kinases is essential for creating the leading edge of cells that migrate in a chemical gradient. Despite the critical relevance to basic and medical science, an understanding of the spatial and temporal regulation of TORC2 and PI3K remains incomplete. An overarching challenge is to decipher how the TORC2 and PI3K signaling pathways are regulated at the front versus the back of cells in a chemical gradient. To explore mechanisms that regulate the TORC2 pathway, we will take advantage of our recently developed biochemical systems. In these systems, chemoattractant-regulated activation and inhibition of TORC2 are faithfully reconstituted with purified TORC2 and two small GTPases, Rho and Ras. These new assays will identify the biochemical and biophysical mechanisms that create distinct chemotactic signaling at the leading and trailing edges of migrating cells. The mechanistic principle that is determined will be tested and translated in our cellular reconstitution systems using knockout cell lines expressing WT and mutant TORC2 and its regulatory components. Using live-cell imaging with FRET microscopy and single-molecule microscopy, we will place the signaling principle in a spatial and temporal context in migrating cells. For the PI3K pathway, we will analyze proteins that control the localization of the PIP3 phosphatase PTEN to the plasma membrane at the back of cells. The rear localization of PTEN enables PIP3 signaling activation at the leading edge and its inhibition at the trailing edge. We will also determine the function of the identified mechanisms that control PTEN localization in tumorigenesis and metastasis in mouse xenograft models expressing engineered PTEN molecules with altered localization. These studies will elucidate the fundamental logics by which polarization of intracellular signaling is established in cells during chemotactic migration and the physiological importance of this signaling in vivo.
总结

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 }}

Miho Iijima其他文献

Miho Iijima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('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:
    $ 40.94万
  • 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:
    $ 40.94万
  • 项目类别:
Regulation of Chemotactic Signaling
趋化信号的调节
  • 批准号:
    10598003
  • 财政年份:
    2019
  • 资助金额:
    $ 40.94万
  • 项目类别:
Regulation of Chemotactic Signaling
趋化信号的调节
  • 批准号:
    10798693
  • 财政年份:
    2019
  • 资助金额:
    $ 40.94万
  • 项目类别:
Regulation of Chemotactic Signaling
趋化信号的调节
  • 批准号:
    10386438
  • 财政年份:
    2019
  • 资助金额:
    $ 40.94万
  • 项目类别:
Lipid Signaling in Chemotaxis
趋化作用中的脂质信号传导
  • 批准号:
    8325132
  • 财政年份:
    2009
  • 资助金额:
    $ 40.94万
  • 项目类别:
Lipid Signaling in Chemotaxis
趋化作用中的脂质信号传导
  • 批准号:
    8887423
  • 财政年份:
    2009
  • 资助金额:
    $ 40.94万
  • 项目类别:
Lipid Signaling in Chemotaxis
趋化作用中的脂质信号传导
  • 批准号:
    8536832
  • 财政年份:
    2009
  • 资助金额:
    $ 40.94万
  • 项目类别:
Lipid Signaling in Chemotaxis
趋化作用中的脂质信号传导
  • 批准号:
    9898604
  • 财政年份:
    2009
  • 资助金额:
    $ 40.94万
  • 项目类别:
Lipid Signaling in Chemotaxis
趋化作用中的脂质信号传导
  • 批准号:
    9100827
  • 财政年份:
    2009
  • 资助金额:
    $ 40.94万
  • 项目类别:

相似海外基金

Defining new asthma phenotypes using high-dimensional data
使用高维数据定义新的哮喘表型
  • 批准号:
    2901112
  • 财政年份:
    2024
  • 资助金额:
    $ 40.94万
  • 项目类别:
    Studentship
Air pollution and Asthma in Canada: Projections of burden and the value of climate adaptation strategies
加拿大的空气污染和哮喘:负担预测和气候适应战略的价值
  • 批准号:
    485322
  • 财政年份:
    2023
  • 资助金额:
    $ 40.94万
  • 项目类别:
    Operating Grants
Data-driven model links BMIz to gene expression in pediatric asthma
数据驱动模型将 BMIz 与小儿哮喘基因表达联系起来
  • 批准号:
    493135
  • 财政年份:
    2023
  • 资助金额:
    $ 40.94万
  • 项目类别:
BIOlogic drug safety and effectiveness interNational pharmacoepidemiologIC study in pregnant women with autoimmune disorders and asthma and their children (BIONIC)
患有自身免疫性疾病和哮喘的孕妇及其子女的生物药物安全性和有效性国际药物流行病学研究(BIONIC)
  • 批准号:
    493526
  • 财政年份:
    2023
  • 资助金额:
    $ 40.94万
  • 项目类别:
    Operating Grants
Engaging Patient and Caregivers in Using Patient-reported Outcomes Measures in Pediatric Clinical Care for Asthma
让患者和护理人员参与儿科哮喘儿科临床护理中患者报告的结果测量
  • 批准号:
    495593
  • 财政年份:
    2023
  • 资助金额:
    $ 40.94万
  • 项目类别:
Basophilic oncostatin M fuels nociceptor neuron-induced asthma
嗜碱性制瘤素 M 促进伤害感受器神经元诱发哮喘
  • 批准号:
    485504
  • 财政年份:
    2023
  • 资助金额:
    $ 40.94万
  • 项目类别:
    Salary Programs
Mechanistic Study of Inspiratory Training in Childhood Asthma
儿童哮喘吸气训练机制研究
  • 批准号:
    10637048
  • 财政年份:
    2023
  • 资助金额:
    $ 40.94万
  • 项目类别:
Early life exposure to metal mixtures: impacts on asthma and lungdevelopment
生命早期接触金属混合物:对哮喘和肺部发育的影响
  • 批准号:
    10678307
  • 财政年份:
    2023
  • 资助金额:
    $ 40.94万
  • 项目类别:
Lung resident Treg suppression of Th2 resident memory T cells in allergic asthma
过敏性哮喘中肺常驻 Treg 对 Th2 常驻记忆 T 细胞的抑制
  • 批准号:
    10664599
  • 财政年份:
    2023
  • 资助金额:
    $ 40.94万
  • 项目类别:
Obesity and Childhood Asthma: The Role of Adipose Tissue
肥胖和儿童哮喘:脂肪组织的作用
  • 批准号:
    10813753
  • 财政年份:
    2023
  • 资助金额:
    $ 40.94万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了