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FASEB SRC on G Protein-Coupled Receptor Kinases and Arrestins: From Structure to Disease

FASEB SRC 关于 G 蛋白偶联受体激酶和抑制蛋白：从结构到疾病

基本信息

批准号：
9330648
负责人：
John Tesmer
金额：
$ 1万
依托单位：
FEDERATION OF AMER SOC FOR EXPER BIOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-06-15 至 2018-06-14
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9330648
关键词：
ADRBK1 gene Adverse effects Angiotensins Animal Model Area Arrestins Behavior Biological Models Biology Blood Pressure Cardiac Cardiovascular Diseases Career Mobility Cell Surface Receptors Cell physiology Cells Cellular biology Collaborations Data Dependency Development Disease Drug Addiction Drug abuse Drug effect disorder Drug usage Endocytosis Funding G Protein-Coupled Receptor Signaling G protein coupled receptor kinase G-Protein-Coupled Receptors G-substrate GTP-Binding Proteins Generations Goals Health Heart failure Heterotrimeric GTP-Binding Proteins Human Hypertension Laboratories Learning Mediating Methodology Methods Morphine Organism Outcome Pain Pathway interactions Pharmaceutical Preparations Pharmacologic Substance Phosphotransferases Physiological Play Process Protein Family Proteins Regulation Research Research Personnel Resources Rest Role Science Scientist Series Signal Pathway Signal Transduction Structure Underrepresented Groups Work addiction combat desensitization drug of abuse inhibitor/antagonist lectures meetings neuroregulation neurotransmission novel novel therapeutic intervention prevent receptor response small molecule symposium

项目摘要

Summary G protein-coupled receptors (GPCRs) and their downstream signaling pathways are important for the regulation of many essential cellular processes and are targets of some of the most commonly prescribed drugs, such as those used to treat pain, heart failure, and high blood pressure (e.g. morphine,  blockers, and angiotensin inhibitors, respectively). GPCR kinases (GRKs) and arrestins work together to regulate GPCR signaling by reducing the ability of receptors to couple with G proteins and by targeting active GPCRs for endocytosis. Although these desensitization mechanisms are important for returning cells to their physiological resting states, GRKs and arrestins are also thought to play prominent roles in addiction and cardiovascular disease, at least in part by instigating other, non-canonical signaling cascades. This proposal seeks funding for a forum that would bring together world-leading researchers who study different aspects of GRK and arrestin biology and their roles in disease called "G Protein-Coupled Receptor Kinases and Arrestins: From Structure to Disease". Two major highlights of the meeting will be keynote lectures by 2012 Nobel laureates who are experts in GPCR, GRK, and arrestin structure, function, and cell biology. The meeting is expected to not only stimulate the generation of new hypotheses, collaborations, and methodologies that can be used to study and combat drug abuse and cardiovascular disease, but also provide career advancement and speaking opportunities for junior investigators and underrepresented groups of scientists.

总结 G蛋白偶联受体（GPCR）及其下游信号通路对于免疫应答是重要的。调节许多基本的细胞过程，是一些最常用的处方的目标药物，如用于治疗疼痛、心力衰竭和高血压的药物（如吗啡、多巴胺受体阻滞剂和血管紧张素抑制剂）。GPCR激酶（GRKs）和抑制蛋白共同作用调节GPCR 通过降低受体与G蛋白偶联的能力和通过靶向活性GPCR来抑制G蛋白的表达，内吞作用尽管这些脱敏机制对于使细胞恢复其生理状态很重要，静息状态、GRK和抑制蛋白也被认为在成瘾和心血管疾病中起重要作用。疾病，至少部分通过煽动其他非经典信号级联。该提案寻求资金，该论坛将汇集世界领先的研究人员，他们研究GRK和arrestin的不同方面 G蛋白偶联受体激酶和抑制蛋白：从结构到功能疾病”。会议的两大亮点将是2012年诺贝尔奖获得者的主题演讲， GPCR、GRK和arrestin结构、功能和细胞生物学专家。预计会议不仅将鼓励产生新的假设，合作和方法，可用于研究和打击药物滥用和心血管疾病，但也提供职业发展和发言为初级研究人员和代表性不足的科学家群体提供机会。