MOLECULAR MECHANISM OF ACTIVATION OF A NOVEL INTRACELLULAR CAMP RECEPTOR

新型细胞内 CAMP 受体激活的分子机制

• 批准号: 8362420
• 负责人: Mark Andrew White
• 金额: $ 0.06万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8362420
• 关键词: Biological Process; Camping; Complex; Cyclic AMP; Cyclic AMP Receptors; Cyclic AMP-Dependent Protein Kinases; Development; Diabetes Mellitus; Disease; Drug Delivery Systems; Eukaryotic Cell; Funding; Grant; Guanine Nucleotide Exchange Factors; Heart failure; Knowledge; Lead; Length; Malignant Neoplasms; Mediating; Molecular; National Center for Research Resources; Physiological; Principal Investigator; Proteins; Radiation; Research; Research Infrastructure; Resources; Signal Pathway; Signal Transduction; Source; Structure; Therapeutic Agents; United States National Institutes of Health; X-Ray Crystallography; cost; improved; novel; receptor; structural biology

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. cAMP-mediated signaling regulates a myriad of important biological processes under physiological conditions and disease states, including diabetes, heart failure and cancer. In eukaryotic cells, the effects of cAMP are mediated by two ubiquitously expressed intracellular cAMP receptors, the classic protein kinase A/cAMP-dependent protein kinase (PKA/cAPK) and the recently discovered exchange protein directly activated by cAMP/cAMP-regulated guanine nucleotide exchange factor (Epac/cAMP-GEF). The existence of two ubiquitously expressed cAMP effectors provides a mechanism for a more precise and integrated control of the cAMP signaling pathways in a spatial and temporal manner. The objective of this proposal is to fill the gap in our current knowledge by solving the crystal structure of full length Epac2-cAMP complex using X-ray crystallography. A better understanding of cAMP-mediated signal transduction could potentially lead to the identification of novel drug targets and the development of new or improved therapeutic agents.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 cAMP介导的信号传导调节生理条件和疾病状态（包括糖尿病、心力衰竭和癌症）下的无数重要生物学过程。在真核细胞中，cAMP的作用由两种广泛表达的细胞内cAMP受体介导，经典的蛋白激酶A/cAMP依赖性蛋白激酶（PKA/cAPK）和最近发现的由cAMP/cAMP调节的鸟嘌呤核苷酸交换因子直接激活的交换蛋白（Epac/cAMP-GEF）。两种普遍表达的cAMP效应物的存在提供了以空间和时间方式更精确和综合控制cAMP信号传导途径的机制。该建议的目的是通过使用X射线晶体学解决全长Epac 2-cAMP复合物的晶体结构来填补我们现有知识中的差距。更好地理解cAMP介导的信号转导可能会导致新的药物靶点的鉴定和新的或改进的治疗剂的开发。