Novel functional domains on adrenoceptors for drug interaction and cell signalling

我们的工作包括研究细胞表面蛋白质（受体），它们对肾上腺素等激素或神经系统中传递信号的物质（神经递质）做出反应。这些受体在协调对压力、疼痛、血压、体温、体液和能量状态变化以及运动等刺激的反应中起着至关重要的作用。它们允许不同器官或神经系统不同部分之间的交流。g蛋白偶联受体（gpcr）是一类与激素和神经递质相互作用的细胞表面受体。许多疾病和病症的治疗依赖于使用选择性激活或阻断单一类型GPCR的药物。事实上，现有的治疗方法中有2-3种是基于这些药物的。在设计新药时，尽可能多地了解靶受体的特性是很重要的。有新的证据表明，细胞内药物、受体和蛋白质之间的相互作用将信号转化为反应（信号蛋白）。例如，受体具有额外的药物作用位点，可以调节其活性，并且还可以与多种信号通路偶联。我们正在研究对肾上腺素和神经递质去甲肾上腺素有反应的肾上腺素受体。我们的研究将使用肾上腺素受体作为模型系统，以确定药物相互作用的新潜在位点，获得这些受体利用的信号机制的新见解，并研究各种磷酸化机制如何影响受体与特定信号通路偶联的能力。

Our work involves studying cell-surface proteins (receptors) that respond to hormones such as adrenaline or substances that transmit signals in the nervous system (neurotransmitters). These receptors play a vital role in orchestrating responses to stimuli such as stress, pain, changes in blood pressure, body temperature, fluid and energy status, and exercise. They allow communication between different organs or different parts of the nervous system. G-protein coupled receptors (GPCRs) are the major group of cell surface receptors that interact with hormones and neurotransmitters. Treatment of many diseases and conditions relies on the use of drugs that selectively activate or block a single type of GPCR. In fact, about 2-3 of existing therapies are based on these drugs. In designing new drugs it is important to understand as much as possible about the properties of the target receptors. There is emerging evidence concerning interactions between drugs, receptors and proteins inside cells that translate signals into responses (signalling proteins). For example, receptors have additional sites of drug action that can modulate their activity, and can also couple to multiple signalling pathways. We are studying adrenoceptors that respond to adrenaline and to the neurotransmitter noradrenaline. Our studies will use adrenoceptors as model systems to identify novel potential sites for drug interaction, to gain new insights into signalling mechanisms utilized by these receptors and to examine how a variety of phosphorylation mechanisms affect the ability of receptors to couple to particular signalling pathways.