Compartmentation of cAMP and Its Coupling to Epac

cAMP 的区室及其与 Epac 的偶联

• 批准号: 7373558
• 负责人: Lisa M. DiPilato
• 金额: $ 4.59万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7373558
• 关键词: 3T3-L1 Cells; Adenylate Cyclase; Adipocytes; Adrenergic Receptor; Apoptosis; Arrestin; Arrestins; Biochemical; Biological Assay; Cell Survival; Cell physiology; Cells; Chronic; Clinical; Condition; Coupling; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Data; Diffuse; Diffusion; Embryo; G protein coupled receptor kinase; Goals; Human; Impairment; In Vitro; Insulin; Kidney; Laboratories; Lead; Life; Localized; Mediating; Mitochondria; Monomeric GTP-Binding Proteins; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Play; Production; Protein Kinase; Proteins; Receptor Signaling; Regulation; Research; Role; Second Messenger Systems; Signal Pathway; Signal Transduction; Site; Specificity; Testing; base; beta-adrenergic receptor; desensitization; desire; novel therapeutics; phosphoric diester hydrolase; response; second messenger; spatiotemporal; tool

The goal of our research is to elucidate the mechanisms that establish cAMP compartmentation in controlling signaling specificity as well as determine the functional importance of cAMP microdomains. cAMP mediates many cellular processes by coupling to downstream effectors such as cAMP dependent protein kinase (PKA) and exchange protein directly activated by cAMP (Epac). Because cAMP is produced at distinct subcellular sites and diffuses rapidly throughout the cell, mechanisms must regulate signal propagation in order to achieve a desired cellular response. However, only recently have tools become available to effectively explore these mechanisms of control. Impaired cAMP signaling has clinical implications such as obesity and type II diabetes. Therefore, a better understanding of cAMP signaling may lead to new therapeutic approaches for these clinical conditions. The specific aims of our reseach are to further develop and characterize FRET-based cAMP indicators to elucidate the spatiotemporal dynamics of beta-adrenergic receptor signaling and use these indicators and in vitro assaysto determine the downstream effectors and functional significance of mitochondrial cAMP.

我们研究的目标是阐明在 cAMP 中建立 cAMP 区室的机制 控制信号传导特异性并确定 cAMP 微结构域的功能重要性。 cAMP 通过与下游效应器（例如 cAMP 依赖性效应器）耦合来介导许多细胞过程 蛋白激酶（PKA）和由 cAMP 直接激活的交换蛋白（Epac）。因为cAMP会产生 在不同的亚细胞位点并在整个细胞中快速扩散，机制必须调节信号 传播以达到所需的细胞反应。然而，直到最近工具才成为 可以有效地探索这些控制机制。 cAMP 信号传导受损具有临床意义 肥胖和二型糖尿病等影响。因此，更好地理解 cAMP 信号传导可能 为这些临床病症带来新的治疗方法。我们研究的具体目标是 进一步开发和表征基于 FRET 的 cAMP 指标，以阐明时空动态 β-肾上腺素能受体信号传导，并使用这些指标和体外测定来确定下游 线粒体 cAMP 的效应器和功能意义。