Novel G-protein coupled receptor interactions and complexes with distinct function and pharmacology

具有独特功能和药理学的新型 G 蛋白偶联受体相互作用和复合物

• 批准号: nhmrc : 212065
• 负责人: Karin Eidne
• 金额: $ 16.45万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2002
• 资助国家: 澳大利亚
• 起止时间: 2002-01-01 至 2004-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/novel-g-protein-function-pharmacology/77784
• 关键词: Novel; protein; coupled; receptor; interactions

G protein coupled receptors (GPCRs) are the target in the human body for most of today's medicines. Almost all pharmaceutical companies market drugs that are GPCR agonists or antagonists aimed at diverse disease states. Our research is focused on the molecular basis of drug recognition and signalling by GPCRs. We use genetic engineering techniques to create new receptors and mutant receptors in order to identify the functional domains of these signalling molecules. We have recently established a novel approach based on proximity-dependent fluorescent technologies to explore receptor interactions and have described the formation of functional G-protein coupled complexes in living cells. This project is to discover new receptor combinations which could potentially affect signalling pathways and redirect cellular responses. Investigation of the mechanisms involved in turning on and off the body s response to stimuli would provide valuable information for drug design and treatment of GPCR-related conditions. We have chosen to use two GPCRs as models for our study of the mechanisms controlling receptor driven cellular responses and the interactions between cellular components-proteins behind this control. Firstly, the gonadotropin releasing hormone receptor (GnRHR), a protein located in the pituitary which is pivotal in the control of reproduction and secondly, the thyrotropin releasing hormone receptor (TRHR), similarly located and involved in modulating thyroid and metabolic function. We will investigate the way these receptors interact with other cellular proteins in order for them to function. Ultimately this will provide a better understanding of how these clinically important proteins function and pave the way for the development of clinical applications that target these receptor systems, resulting in the effective treatment of a wide range of conditions and diseases, including pain, migraine, certain forms of cancer, neurological and reproductive disorders.

G 蛋白偶联受体 (GPCR) 是当今大多数药物的人体内靶点。几乎所有制药公司都销售针对不同疾病状态的 GPCR 激动剂或拮抗剂药物。我们的研究重点是 GPCR 药物识别和信号传导的分子基础。我们使用基因工程技术来创建新的受体和突变受体，以识别这些信号分子的功能域。我们最近建立了一种基于邻近依赖性荧光技术的新方法来探索受体相互作用，并描述了活细胞中功能性 G 蛋白偶联复合物的形成。该项目旨在发现可能影响信号传导途径并重定向细胞反应的新受体组合。研究开启和关闭身体对刺激反应的机制将为药物设计和 GPCR 相关疾病的治疗提供有价值的信息。我们选择使用两个 GPCR 作为模型来研究控制受体驱动的细胞反应的机制以及这种控制背后的细胞成分-蛋白质之间的相互作用。首先是促性腺激素释放激素受体（GnRHR），这是一种位于垂体中的蛋白质，在控制生殖中至关重要；其次是促甲状腺激素释放激素受体（TRHR），其位置相似并参与调节甲状腺和代谢功能。我们将研究这些受体与其他细胞蛋白质相互作用的方式，以使它们发挥作用。最终，这将有助于更好地了解这些临床上重要的蛋白质如何发挥作用，并为针对这些受体系统的临床应用的开发铺平道路，从而有效治疗多种病症和疾病，包括疼痛、偏头痛、某些形式的癌症、神经和生殖疾病。