Montreal Heart Institute, Montréal, Québec, Canada.
Am J Physiol Heart Circ Physiol. 2011 Nov;301(5):H1754-64. doi: 10.1152/ajpheart.00657.2011. Epub 2011 Sep 2.
In recent years, we have come to appreciate the complexity of G protein-coupled receptor signaling in general and β-adrenergic receptor (β-AR) signaling in particular. Starting originally from three β-AR subtypes expressed in cardiomyocytes with relatively simple, linear signaling cascades, it is now clear that there are large receptor-based networks which provide a rich and diverse set of responses depending on their complement of signaling partners and the physiological state. More recently, it has become clear that subcellular localization of these signaling complexes also enriches the diversity of phenotypic outcomes. Here, we review our understanding of the signaling repertoire controlled by nuclear β-AR subtypes as well our understanding of the novel roles for G proteins themselves in the nucleus, with a special focus, where possible, on their effects in cardiomyocytes. Finally, we discuss the potential pathological implications of alterations in nuclear β-AR signaling.
近年来，我们逐渐认识到 G 蛋白偶联受体信号转导的复杂性，尤其是β-肾上腺素能受体（β-AR）信号转导。最初从心肌细胞中表达的三种β-AR 亚型开始，其信号转导途径相对简单且呈线性，现在已经很清楚，存在着大型的受体基础网络，这些网络根据其信号转导伙伴的组成和生理状态提供了丰富多样的反应。最近，人们越来越清楚的是，这些信号转导复合物的亚细胞定位也丰富了表型结果的多样性。在这里，我们回顾了我们对核β-AR 亚型控制的信号转导谱的理解，以及我们对 G 蛋白本身在核内的新作用的理解，特别关注它们在心肌细胞中的作用。最后，我们讨论了核β-AR 信号转导改变的潜在病理意义。
