Regulators of G protein signalling on the Golgi complex

细胞中蛋白质的分泌涉及一系列调节和信号蛋白。G蛋白是位于高尔基体膜上的信号转导蛋白，参与分泌途径中运输小泡的萌发。一个新发现的G蛋白信号(RGS)调节蛋白家族发挥着关闭G蛋白产生的信号的关键功能。RGS蛋白功能强大，但到目前为止，调节分子的定义还不明确。在这项研究中，我们将鉴定和鉴定位于高尔基体膜上的巨噬细胞中的RGS蛋白，并帮助调节细胞因子的分泌和其他免疫功能。对选定的RGS蛋白质的更详细的研究将包括对蛋白质内功能区域的突变分析，以及识别与RGS蛋白质相互作用的其他蛋白质。总体而言，这些研究将引导我们了解特定的RGS蛋白如何与G蛋白和其他分子相互作用，以调节分泌途径中的信号传递。细胞信号的异常会在多种疾病中造成严重后果，并可能导致癌症。同样，细胞中的异常分泌也会导致炎症、糖尿病和其他疾病过程。从我们对RGS蛋白的研究中获得的信息将具有广泛的影响，并有可能揭示这些疾病的治疗新靶点。

The secretion of proteins from cells involves a host of regulatory and signalling proteins. G proteins, signal transducers, located on the Golgi membranes, participate in the budding of transport vesicles in the secretory pathway. A newly-discovered family of Regulators of G Protein Signalling (RGS) proteins perform the critical function of turning off signals generated by G proteins. RGS proteins are powerful, but as yet, ill-defined regulatory molecules. In this study we will identify and characterize RGS proteins in macrophages that are located on Golgi membranes and help to regulate cytokine secretion and other immune functions. More detailed studies on selected RGS proteins will include mutational analysis of functional domains within the proteins and identification of other proteins that interact with RGS proteins. Overall these studies will lead us to understand how specific RGS proteins interact with G proteins and other molecules to regulate signalling in the secretory pathway. Anomalies in cell signalling have severe consequences in a variety of diseases and can cause cancer. Similarly, abnormal secretion in cells contributes to inflammation, diabetes and other disease processes. Information forthcoming from our studies on RGS proteins will have wide-reaching implications and the potential to reveal new targets for therapeutics in these diseases.