Department of Neuro and Sensory Physiology, University of Göttingen, Göttingen, Germany.
Curr Mol Pharmacol. 2009 Nov;2(3):237-48. doi: 10.2174/1874467210902030237.
The superfamily of G protein coupled receptors (GPCRs) comprises the largest group of cell surface receptors expressed by the human genome. Accordingly, these receptors are the target of a substantial portion of current pharmaceuticals. Over the past few decades there have been many substantial discoveries regarding GPCRs structure and function that have led to the current understanding of the complexity of the signal transduction which these receptors initiate. What was once generally believed to be a simple linear pathway, has become one with manifold bifurcations and multiple regulatory and feedback mechanisms. In the following we review the fundamental ground work upon which this field of research was established and the work that has more recently begun to uncover the complexity of GPCR signaling. The emerging signaling paradigm includes (i) the capacity of one receptor to couple to and initiate pathways through multiple G proteins, (ii) the capability of one G protein to activate many effectors, as well as (iii) the ability of a GPCR to transduce signals through G protein independent pathways. We also briefly touch upon some implications of GPCR oligomerization and discuss signaling cascades of two serotonin receptors, 5-HT(4) and 5-HT(7), whose pathways exemplify the richness and complexity of GPCR signaling mechanisms.
G 蛋白偶联受体（GPCRs）超家族是人类基因组表达的最大细胞表面受体群。相应地，这些受体是当前大部分药物的靶点。在过去的几十年中，人们对 GPCR 的结构和功能有了许多重大发现，这些发现使人们对这些受体启动的信号转导的复杂性有了当前的认识。曾经被普遍认为是一个简单的线性途径，现在已经变成了一个具有多种分支和多个调节和反馈机制的途径。在下面的内容中，我们将回顾该研究领域建立的基础工作，以及最近开始揭示 GPCR 信号转导复杂性的工作。新兴的信号转导范例包括：（i）一个受体与多种 G 蛋白偶联并启动途径的能力；（ii）一种 G 蛋白激活多种效应器的能力；以及（iii）GPCR 通过 G 蛋白独立途径转导信号的能力。我们还简要讨论了 GPCR 寡聚化的一些影响，并讨论了两种血清素受体 5-HT（4）和 5-HT（7）的信号级联反应，它们的途径体现了 GPCR 信号转导机制的丰富性和复杂性。
