Techniques: promiscuous Galpha proteins in basic research and drug discovery

Trends Pharmacol Sci. 2005 Nov;26(11):595-602. doi: 10.1016/ Epub 2005 Sep 23.


Assay technologies that measure the activation of heterotrimeric (alphabetagamma) G proteins by G-protein-coupled receptors (GPCRs) are well established within the pharmaceutical industry, either for pharmacological characterization or for the identification of natural or surrogate receptor ligands. Despite recent evidence indicating that GPCR-linked signalling events might not be mediated exclusively by G proteins, G-protein activation remains a common benchmark for assessing GPCR family members. Thus, assay systems that translate ligand-mediated modulation of GPCRs into G-protein-dependent intracellular responses still represent key components of both basic research and the drug discovery process. In this article, the current knowledge and recent progress of integrating Galpha subunits into assay systems for GPCR drug discovery will be reviewed. Emphasis is given to novel promiscuous and chimeric Galpha proteins. Because of their ability to interact with a wide range of GPCRs, such novel G proteins are likely to be incorporated rapidly into drug discovery programmes.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Biosensing Techniques
  • Calcium Signaling / drug effects
  • Calcium Signaling / physiology
  • Cell Line
  • Drug Design
  • GTP-Binding Protein alpha Subunits / chemistry*
  • GTP-Binding Protein alpha Subunits / genetics
  • GTP-Binding Protein alpha Subunits / metabolism*
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • Heterotrimeric GTP-Binding Proteins / chemistry
  • Heterotrimeric GTP-Binding Proteins / genetics
  • Heterotrimeric GTP-Binding Proteins / metabolism
  • Humans
  • Ligands
  • Molecular Sequence Data
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / genetics
  • Receptors, Serotonin / metabolism
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology
  • Transfection


  • GTP-Binding Protein alpha Subunits
  • Ligands
  • Receptors, G-Protein-Coupled
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • serotonin 6 receptor
  • G protein alpha 16
  • GNA14 protein, human
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • Heterotrimeric GTP-Binding Proteins