FASEB SRC: The G Protein-coupled Receptor Kinases and Arrestins Conference: Key Modulators of Signal Transduction

项目摘要 G蛋白偶联受体(GPCRs)及其下游信号通路对 调节许多基本的细胞过程，是一些最常用的处方的靶点 药物，如用于治疗疼痛、心力衰竭和高血压的药物(如吗啡、β阻滞剂和 分别为血管紧张素抑制剂)。GPCRK和拦阻蛋白是GPCRs的关键调节因子 发信号。它们协同作用，通过降低受体的偶联能力来促进受体脱敏 通过G蛋白和靶向活性GPCRs进行内吞作用。尽管这些脱敏机制 对细胞恢复生理休眠状态很重要，GRK和拦阻蛋白也是已知的 鼓动非规范的信号。在这一点上，这些蛋白质在中枢神经和 心血管系统，特别是药物成瘾和心力衰竭等疾病。这 一项提案寻求为一个论坛提供资金，该论坛将汇聚研究不同领域的世界领先研究人员 GRK和arrestin的生物学特性及其在G蛋白偶联受体激酶疾病中的作用 和阻滞剂：信号转导的关键调制器“。会议的两个主要亮点将是两个主旨 讲师是GPCR、GRK和arrestin结构、功能和细胞生物学方面的专家。此外，高级 初级科学家将能够向该领域的领导者展示他们最新和未发表的工作，这 应该刺激产生新的假设和方法论，并有望导致 可用于研究和抗击药物滥用和心血管疾病的合作。这将是一个 学员获得批判性反馈并建立重要联系的绝佳机会，这将 有利于他们的事业发展。

Project 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, β blockers, and angiotensin inhibitors, respectively). GPCR kinases (GRKs) and arrestins are key regulators of GPCR signaling. They act in tandem to promote receptor desensitization 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 known to instigate non-canonical signaling. In this regard, these proteins play prominent roles in the central nervous and cardiovascular systems, and especially in diseases such as drug addiction and heart failure, respectively. 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: Key Modulators of Signal Transduction". Two major highlights of the meeting will be two keynote lectures who are experts in GPCR, GRK, and arrestin structure, function, and cell biology. In addition, senior and junior scientists will be able to present their most recent and unpublished work to leaders in the field, which should stimulate the generation of new hypotheses and methodologies and hopefully lead to the beginning of collaborations that can be used to study and combat drug abuse and cardiovascular disease. This will be a great opportunity for trainees to get critical feedback and make important connections, which will benefit their career advancement.