Bioluminescence resonance energy transfer (BRET) has advantages over Förster resonance energy transfer (FRET), particularly for high-throughput screening. Like its cousin, the luminescence-based technique can be used in real-time quantitative assays of living cells. Furthermore, it has proved valuable for studying tyrosine kinase receptors, which are important drug targets because defective or overactive receptors cause several diseases, including diabetes and cancer. Researchers from Université Paris Descartes have studied BRET as a method for analyzing the receptors. Their review primarily details recent experiments demonstrating the efficacy of the method for investigating insulin and insulin growth factor-1 receptors as model tyrosine kinases. A chief advantage of the technique is that it can show conformational changes in the receptors.The reviewers emphasize the advantages of BRET versus FRET. The former technique involves the transfer of energy from a luminescent donor to a fluorescent acceptor, whereas the latter requires two fluorophores with overlapping absorption and emission spectra. The overlapping spectra can confound experimental results because the acceptor often is excited directly by the light intended to stimulate the donor. Furthermore, exciting the donor fluorophore can cause photobleaching, whereas a luminescent protein does not have that problem because it does not require photostimulation.The authors state that BRET is superior to FRET for high-throughput screening. BRET-based high-throughput screening assays have been created with 10 times more sensitivity than otherwise identical assays made with FRET. However, the latter technique currently has a higher spatial resolution, so it is now better for imaging protein-protein interactions, but the reviewers predict that improvements to detectors will make the former the method of choice for this application as well.They underline the advantages of BRET compared with other methods for high-throughput screening of tyrosine kinase receptors. They note that the technique requires only one low-cost reagent and no tedious washing steps or separations. No radioactivity is involved, and it does not require a phosphorylation reaction. (Expert Opinion Therapeutic Targets, April 2007, pp. 541-556.)