Escribá Pablo V, Wedegaertner Philip B, Goñi Félix M, Vögler Oliver
Laboratory of Molecular and Cellular Biomedicine, Institut Universitari d'Investigació en Ciències de la Salut, Department of Biology, University of the Balearic Islands, Palma de Mallorca, Spain.
Biochim Biophys Acta. 2007 Apr;1768(4):836-52. doi: 10.1016/j.bbamem.2006.09.001. Epub 2006 Sep 16.
Signal transduction via G-protein-coupled receptors (GPCRs) is a fundamental pathway through which the functions of an individual cell can be integrated within the demands of a multicellular organism. Since this family of receptors first discovered, the proteins that constitute this signaling cascade and their interactions with one another have been studied intensely. In parallel, the pivotal role of lipids in the correct and efficient propagation of extracellular signals has attracted ever increasing attention. This is not surprising given that most of the signal transduction machinery is membrane-associated and therefore lipid-related. Hence, lipid-protein interactions exert a considerable influence on the activity of these proteins. This review focuses on the post-translational lipid modifications of GPCRs and G proteins (palmitoylation, myristoylation, and isoprenylation) and their significance for membrane binding, trafficking and signaling. Moreover, we address how the particular biophysical properties of different membrane structures may regulate the localization of these proteins and the potential functional consequences of this phenomenon in signal transduction. Finally, the interactions that occur between membrane lipids and GPCR effector enzymes such as PLC and PKC are also considered.
通过G蛋白偶联受体（GPCRs）进行的信号转导是一条基本途径，通过该途径单个细胞的功能可以整合到多细胞生物体的需求中。自从首次发现这类受体以来，构成该信号级联反应的蛋白质及其相互作用就受到了深入研究。与此同时，脂质在细胞外信号正确有效传播中的关键作用也越来越受到关注。鉴于大多数信号转导机制都与膜相关，因此与脂质有关，这并不奇怪。因此，脂-蛋白相互作用对这些蛋白质的活性有相当大的影响。本综述重点关注GPCRs和G蛋白的翻译后脂质修饰（棕榈酰化、肉豆蔻酰化和异戊二烯化）及其对膜结合、转运和信号传导的意义。此外，我们探讨了不同膜结构的特定生物物理特性如何调节这些蛋白质的定位以及这种现象在信号转导中的潜在功能后果。最后，还考虑了膜脂与GPCR效应酶（如PLC和PKC）之间发生的相互作用。
