Lipid-protein interactions in GPCR-associated signaling

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Membrane / chemistry
  • Cell Membrane / metabolism
  • Heterotrimeric GTP-Binding Proteins / chemistry
  • Heterotrimeric GTP-Binding Proteins / metabolism*
  • Humans
  • Membrane Lipids / chemistry
  • Membrane Lipids / metabolism*
  • Receptors, G-Protein-Coupled / chemistry
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction*


  • Membrane Lipids
  • Receptors, G-Protein-Coupled
  • Heterotrimeric GTP-Binding Proteins