Structure function studies in intestinal epithelial JAM
肠上皮JAM的结构功能研究
基本信息
- 批准号:8451327
- 负责人:
- 金额:$ 44.47万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2002
- 资助国家:美国
- 起止时间:2002-05-01 至 2016-04-30
- 项目状态:已结题
- 来源:
- 关键词:ActomyosinAffectAtomic Force MicroscopyAttenuatedBackBindingBiochemicalBiological AssayCell LineCell ProliferationCell membraneCell surfaceCellsCo-ImmunoprecipitationsComplementCrohn&aposs diseaseCytoskeletonDimerizationDiseaseDown-RegulationDrug Delivery SystemsElementsEndocytosisEpithelialEpithelial CellsEventFundingGoalsHandHomeostasisHumanImaging TechniquesIn VitroInflammationInflammatory disease of the intestineInjuryIntegrinsIntercellular JunctionsIntestinesJAM proteinKnowledgeLightLinkMediatingMessenger RNAMonomeric GTP-Binding ProteinsMusMutagenesisPathologicPermeabilityPlayProteinsProto-Oncogene Proteins c-aktRecombinantsRecoveryRecyclingRegulationRoleSeriesSignal PathwaySignal TransductionSiteStructureTechniquesTestingTight JunctionsUlcerUlcerative ColitisVaccinesWound Healingafadinbasebeta catenincell motilityimprovedin vivoinhibitor/antagonistinnovationintestinal homeostasisknockout animalmigrationmutantnovelprotein expressionprotein transportrab GTP-Binding Proteinsresearch studyresponsescaffoldtherapeutic targettraffickingtumor progressionwound
项目摘要
DESCRIPTION (provided by applicant): A central theme of this proposal is based on the evolving concept that tight junction (TJ) proteins do not function simply as static, physical barrir forming elements but as signaling centers that regulate critical homeostatic functions within intestinal epithelial cells. This concept is consistent with findings in humans that have condition associated with dysregulated intestinal homeostasis such as ulcerative colitis and Crohn's Disease where altered TJ protein expression is associated with defective intestinal epithelial barrier function and extensive mucosal ulceration/wounding. The goal of this proposal is centered on elucidating fundamental mechanisms of how the tight junction protein JAM-A signals to control epithelial barrier and cell migration. It will specifically focus on identifyingnovel proximal signaling elements linked to JAM-A that regulate barrier during junctional assembly and during the steady state (Aim 1). It will also focus on elucidating how JAM-A regulates cell migration through effects on beta 1 integrin dynamics at the level of protein trafficking and small
GTPase signaling. We have demonstrated that JAM-A mediated regulation of cell migration and barrier are dependent on dimerization of JAM-A in a cis configuration within the same cell. In aim 3 of this proposal, we will extend these important findings to determine the role of dimerization of JAM-A between cells in trans and if such interactions play a role in regulating cell migration and barrier. Knowledge gained from these studies will not only shed new light into mechanisms of outside-in signaling at the TJ that regulate permeability, migration and proliferation, but may also provide new ideas for therapeutic targets with diverse applications ranging from enhanced vaccine/drug delivery to wound healing/anti-inflammation or inhibition of cancer progression.
描述(由申请人提供):该提案的中心主题是基于以下不断发展的概念:紧密连接(TJ)蛋白不仅作为静态的物理屏障形成元件发挥作用,而且作为调节肠上皮细胞内关键稳态功能的信号传导中心发挥作用。这一概念与患有与失调的肠内稳态相关的病症的人类中的发现一致,所述病症例如溃疡性结肠炎和克罗恩病,其中改变的TJ蛋白表达与缺陷的肠上皮屏障功能和广泛的粘膜溃疡/创伤相关。该提案的目标集中在阐明紧密连接蛋白JAM-A如何信号控制上皮屏障和细胞迁移的基本机制。它将特别关注识别与JAM-A相关的新型近端信号元件,这些元件在连接组装和稳态期间调节屏障(Aim 1)。它还将侧重于阐明JAM-A如何通过在蛋白质运输和小分子水平上对β 1整合素动力学的影响来调节细胞迁移。
GT3信号。我们已经证明,JAM-A介导的细胞迁移和屏障的调节依赖于同一细胞内顺式构型的JAM-A的二聚化。在本提案的目标3中,我们将扩展这些重要的发现,以确定JAM-A在反式细胞之间的二聚化作用,以及这种相互作用是否在调节细胞迁移和屏障中发挥作用。从这些研究中获得的知识不仅将为TJ调节渗透性,迁移和增殖的由外向内信号传导机制提供新的见解,而且还可能为具有不同应用的治疗靶点提供新思路,从增强疫苗/药物递送到伤口愈合/抗炎或抑制癌症进展。
项目成果
期刊论文数量(0)
专著数量(0)
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会议论文数量(0)
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CHARLES A PARKOS其他文献
CHARLES A PARKOS的其他文献
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{{ truncateString('CHARLES A PARKOS', 18)}}的其他基金
Structure function studies in intestinal epithelial JAM
肠上皮JAM的结构功能研究
- 批准号:
7898173 - 财政年份:2009
- 资助金额:
$ 44.47万 - 项目类别:
Neutrophil interactions with intestinal epithelial cells
中性粒细胞与肠上皮细胞的相互作用
- 批准号:
7847792 - 财政年份:2009
- 资助金额:
$ 44.47万 - 项目类别:
Role of signal regulatory protein in neutrophil function
信号调节蛋白在中性粒细胞功能中的作用
- 批准号:
7086257 - 财政年份:2003
- 资助金额:
$ 44.47万 - 项目类别:
Emory Epithelial Pathobiology Research Development Center
埃默里大学上皮病理学研究发展中心
- 批准号:
8288323 - 财政年份:2003
- 资助金额:
$ 44.47万 - 项目类别:
Role of signal regulatory protein in neutrophil function
信号调节蛋白在中性粒细胞功能中的作用
- 批准号:
6936644 - 财政年份:2003
- 资助金额:
$ 44.47万 - 项目类别:
Emory Epithelial Pathobiology Research Development Center
埃默里大学上皮病理学研究发展中心
- 批准号:
8080876 - 财政年份:2003
- 资助金额:
$ 44.47万 - 项目类别:
Role of signal regulatory protein in neutrophil function
信号调节蛋白在中性粒细胞功能中的作用
- 批准号:
6684457 - 财政年份:2003
- 资助金额:
$ 44.47万 - 项目类别:
Role of signal regulatory protein in neutrophil function
信号调节蛋白在中性粒细胞功能中的作用
- 批准号:
6765880 - 财政年份:2003
- 资助金额:
$ 44.47万 - 项目类别:
Structure function studies in intestinal epithelial JAM
肠上皮JAM的结构功能研究
- 批准号:
8662243 - 财政年份:2002
- 资助金额:
$ 44.47万 - 项目类别:
Intestinal Inflammation: Signaling proteins and the rate of PMN transmigration
肠道炎症:信号蛋白和 PMN 迁移率
- 批准号:
10428645 - 财政年份:2002
- 资助金额:
$ 44.47万 - 项目类别:
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