Src Regulation of Lung Endothelial Barrier Function
Src 对肺内皮屏障功能的调节
基本信息
- 批准号:8059132
- 负责人:
- 金额:$ 33.47万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-03-01 至 2016-02-29
- 项目状态:已结题
- 来源:
- 关键词:1-Phosphatidylinositol 3-KinaseAddressAdhesionsAdult Respiratory Distress SyndromeAffinityAlbuminsBindingBiochemicalBlood VesselsCaveolaeCell membraneCellular biologyCouplingDataDynamin 2EdemaEndothelial CellsEventGene DeletionGoalsImageInflammatoryInflammatory ResponseIntercellular adhesion molecule 1LeadLungMediatingModificationMusOxidantsPTPN11 genePathway interactionsPermeabilityPhosphatidylinositolsPhosphorylationPhysiologicalPost-Translational Protein ProcessingProtein BiosynthesisProtein DephosphorylationProtein KinaseProtein Tyrosine PhosphatasePulmonary CirculationPulmonary EdemaPulmonary vesselsRecruitment ActivityRegulationRoleSecondary toSignal PathwaySignal TransductionSignal Transduction PathwaySiteTestingTimeTranslationsbasecaveolin 1cytokinefeedingfilaminlung injurylung vascular injurymolecular imagingneutrophilnew therapeutic targetnovelprotein kinase C zetatranscytosisuptake
项目摘要
In Project 4, we will test the hypotheses that (i) Nox2-dependent oxidant signaling activates Src kinasedependent
ICAM-1-phosphorylation and thereby the recruitment of PMNs in the pulmonary circulation, and that
(ii) Src phosphorylation of ICAM-1 in turn protracts Src activation and phosphorylation of caveolin-1 and
dynamin-2, thereby triggering caveolae-mediated transcytosis of albumin and endothelial hyper-permeability.
These studies will address the following Specific Aims: (1) role of PI3-kinase, PKC zeta, Nox2, and Src
signaling, and of Akt phosphorylation of filamin A in the mechanism of ICAM-1 phosphorylation, clustering, and
rapid increase in ICAM-1 binding affinity in lung microvascular endothelial cells and PMN uptake in lungs; (2)
role of phospho-ICAM-1 in recruitment of SHP2 and protracting Src activation and thereby caveolin-1 and
dynamin-2 activation, and thus stimulating caveolae-mediated transcytosis and hyper-permeability of albumin.
Project 4 will delineate the signaling mechanisms mediating the post-translafional modification of ICAM-1 in
pulmonary microvessel endothelial cells using imaging, cell biology, biochemical, and physiological
approaches. We will thereby establish how endothelial cell ICAM-1 shifts to a high-affinity state and promotes
PMN adhesion and sequestration and also induces caveolae-mediated hyper-permeability via the transcytosis
of albumin. These studies it is hoped will lead to a new understanding of the early PMN-mediated lung
inflammatory response and its coupling to lung vascular hyper-permeability. Identification of the key signaling
hubs of ICAM-1-mediated endothelial adhesivity and activation of the caveolae-mediated albumin transport
pathway is likely to provide novel therapeutic targets directed against infiammatory lung injury.
在项目4中,我们将测试(i) nox2依赖的氧化信号激活Src激酶依赖的假设
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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RICHARD D MINSHALL其他文献
RICHARD D MINSHALL的其他文献
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{{ truncateString('RICHARD D MINSHALL', 18)}}的其他基金
Fibroblast Mediated Mechanisms of Pulmonary Hypertension
成纤维细胞介导的肺动脉高压机制
- 批准号:
10163897 - 财政年份:2019
- 资助金额:
$ 33.47万 - 项目类别:
Fibroblast Mediated Mechanisms of Pulmonary Hypertension
成纤维细胞介导的肺动脉高压机制
- 批准号:
10378641 - 财政年份:2019
- 资助金额:
$ 33.47万 - 项目类别:
Fibroblast Mediated Mechanisms of Pulmonary Hypertension
成纤维细胞介导的肺动脉高压机制
- 批准号:
10599245 - 财政年份:2019
- 资助金额:
$ 33.47万 - 项目类别:
Fibroblast Mediated Mechanisms of Pulmonary Hypertension
成纤维细胞介导的肺动脉高压机制
- 批准号:
9912845 - 财政年份:2019
- 资助金额:
$ 33.47万 - 项目类别:
Caveolin-1 and NO Regulate PMN-mediated Increases in Vascular Permeability
Caveolin-1 和 NO 调节 PMN 介导的血管通透性增加
- 批准号:
7822536 - 财政年份:2009
- 资助金额:
$ 33.47万 - 项目类别:
Src Regulation of Lung Endothelial Barrier Function
Src 对肺内皮屏障功能的调节
- 批准号:
7367823 - 财政年份:2007
- 资助金额:
$ 33.47万 - 项目类别:
Src Regulation of Lung Endothelial Barrier Function
Src 对肺内皮屏障功能的调节
- 批准号:
7312502 - 财政年份:2006
- 资助金额:
$ 33.47万 - 项目类别:
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