Setting up a bioluminescence resonance energy transfer high throughput screening assay to search for protein/protein interaction inhibitors in mammalian cells

Frontiers in Endocrinology

Volumn 3, Issue SEP, 2012, Pages

  Couturier, Cyril ^a,b,c,d   Deprez, Benoit ^a,b,c,d  

^a UNIV LILLE   (France)

^b INSERM   (France)

^c INSTITUT PASTEUR DE LILLE   (France)

^d PRIM Pôle de Recherche Interdisciplinaire sur le Médicament   (France)

Author keywords

BRET; HTS; Inhibitor compound; Modulator compound; P2i2; PPI; RET; Screening assay

Indexed keywords

EID: 84874368741     PISSN: None     EISSN: 16642392     Source Type: Journal    
DOI: 10.3389/fendo.2012.00100     Document Type: Review

References (116)

1. Algar, W. R., Tavares, A. J., and Krull, U. J. (2010). Beyond labels: a review of the application of quantum dots as integrated components of assays, bioprobes, and biosensors utilizing optical transduction. Anal. Chim. Acta 673, 1-25.
2. Alvarez-Curto, E., Pediani, J. D., and Milligan, G. (2010). Applications of fluorescence and biolumines-cence resonance energy transfer to drug discovery at G protein coupled receptors. Anal. Bioanal. Chem. 398, 167-180.
3. Arai, R., Nakagawa, H., Kitayama, A., Ueda, H., and Nagamune, T. (2002). Detection of protein-protein interaction by bioluminescence resonance energy transfer from firefly luciferase to red fluorescent protein. J. Biosci. Bioeng. 94, 362-364.
4. Arai, R., Nakagawa, H., Tsumoto, K., Mahoney, W., Kumagai, I., Ueda, H., and Nagamune, T. (2001). Demonstration of a homogeneous noncompetitiveimmunoassay based on bioluminescence resonance energy transfer. Anal. Biochem. 289, 77-81.
5. Audet, M., Lagacé, M., Silversides, D. W., and Bouvier,M. (2010). Protein-protein interactions monitored in cells from transgenic mice using bioluminescence resonance energy transfer. FASEB J. 24, 2829-2838.
6. Audet, N., and Piñeyro, G. (2011). Using BRET to detect ligand-specific conformational changes in preformed signalling complexes. Methods Mol. Biol. 756, 149-163.
7. Ayoub, M. A., Couturier, C., Lucas-Meunier, E., Angers, S., Fossier, P., Bouvier, M., and Jockers, R. (2002). Monitoring of ligand-independent dimerization and ligand-induced conformational changes of mela-tonin receptors in living cells by bioluminescence resonance energy transfer. J. Biol. Chem. 277, 21522-21528.
8. Ayoub, M. A., Levoye, A., Delagrange, P., and Jockers, R. (2004). Preferential formation of MT1/MT2 melatonin receptor heterodimers with distinct ligand interaction properties compared with MT2 homodimers. Mol. Pharmacol. 66, 312-321.
9. Ayoub, M. A., and Pfleger, K. D. G. (2010). Recent advances in biolu-minescence resonance energy transfer technologies to study GPCR heteromerization. Curr. Opin. Pharmacol. 10, 44-52.
10. Bacart, J., Corbel, C., Jockers, R., Bach, S., and Couturier, C. (2008). The BRET technology and its application to screening assays. Biotechnol. J. 3, 311-324.
11. Bacart,J., Leloire,A., Levoye,A.,Froguel, P., Jockers, R., and Couturier, C. (2010). Evidence for leptin receptor isoforms heteromerization at the cell surface. FEBS Lett. 584, 2213-2217.
12. Bader, S., Kühner, S., and Gavin, A.-C. (2008). Interaction networks for systems biology. FEBS Lett. 582, 1220-1224.
13. Blanquart, C., Gonzalez-Yanes, C., and Issad, T. (2006). Monitoring the activation state of insulin/insulinlike growth factor-1 hybrid receptors using bioluminescence resonance energy transfer. Mol. Pharmacol. 70, 1802-1811.
14. Boubekeur, S., Boute, N., Pagesy, P., Zilberfarb, V., Christeff, N., and Issad, T. (2011). A new highly efficient substrate-trapping mutant of protein tyrosine phosphatase 1B (PTP1B) reveals full autoactivation of the insulin receptor precursor. J. Biol. Chem. 286, 19373-19380.
15. Boute, N., Boubekeur, S., Lacasa, D., and Issad, T. (2003). Dynamics of the interaction between the insulin receptor and protein tyrosine-phosphatase 1B in living cells. EMBO Rep. 4, 313-319.
16. Boute, N., Jockers, R., and Issad, T. (2002). The use of resonance energy transfer in high-throughput screen-ing:BRET versus FRET.Trends Pharmacol. Sci. 23, 351-354.
17. Boute, N., Pernet, K., and Issad, T. (2001). Monitoring the activation state of the insulin receptor using bioluminescence resonance energy transfer. Mol. Pharmacol. 60, 640-645.
18. Brovko, L. Y., and Griffiths, M. W. (2007). Illuminating cellular physiology: recent developments. Sci. Prog. 90, 129-160.
19. Chan,F.K.-M. (2004). Monitoring molecular interactions in living cells usingflow cytometric analysis of fluorescence resonance energy transfer. Methods Mol. Biol. 261, 371-382.
20. Charest, P. G., Terrillon, S., and Bou-vier, M. (2005). Monitoring agonist-promoted conformational changes of beta-arrestin in living cells by intramolecular BRET. EMBO Rep. 6, 334-340.
21. Chautard, E., Thierry-Mieg, N., and Ricard-Blum, S. (2009). Interaction networks: from protein functions to drug discovery. Pathol. Biol. (Paris) 57, 324-333.
22. Chen, X., Liu, M.-X., and Yan, G.-Y. (2012). Drug-target interaction prediction by random walk on the heterogeneous network. Mol. Biosyst. Available at: http:// www.ncbi.nlm.nih.gov/pubmed/ 22538619 (accessed May 18, 2012).
23. Clackson, T. (1997). Controlling mammalian gene expression with small molecules. Curr. Opin. Chem. Biol. 1, 210-218.
24. Corbel, C., Wang, Q., Bousserouel, H., Hamdi, A., Zhang, B., Lozach, O., Ferandin, Y., Tan, V. B. C., Guéritte, F., Colas, P., Couturier, C., and Bach, S. (2011). First BRET-based screening assay performed in budding yeast leads to the discovery of CDK5/p25 interaction inhibitors. Biotechnol. J. 6, 860-870.
25. Coulon, V., Audet, M., Homburger, V., Bockaert, J., Fagni, L., Bouvier, M., and Perroy, J. (2008). Subcellular imaging of dynamic protein interactions by bioluminescence resonance energy transfer. Biophys. J. 94, 1001-1009.
26. Couturier, C., and Jockers, R. (2003). Activation of the leptin receptor by a ligand-induced conforma-tional change of constitutive receptor dimers. J. Biol. Chem. 278, 26604-26611.
27. Couturier, C., Sarkis, C., Séron, K., Belouzard, S., Chen, P., Lenain, A., Corset, L., Dam, J., Vau-thier, V., Dubart, A., Mallet, J., Froguel, P., Rouillé, Y., and Jock-ers, R. (2007). Silencing of OB-RGRP in mouse hypothalamic arcuate nucleus increases leptin receptor signaling and prevents diet-induced obesity. Proc. Natl. Acad. Sci. U.S.A. 104, 19476-19481.
28. Dacres, H., Dumancic, M. M., Horne, I., and Trowell, S. C. (2009). Direct comparison of bioluminescence-based resonance energy transfer methods for monitoring of prote-olytic cleavage. Anal. Biochem. 385, 194-202.
29. Dacres, H., Michie, M., and Trow-ell, S. C. (2012). Comparison of enhanced bioluminescence energy transfer donors for protease biosensors. Anal. Biochem. 424, 206-210.
30. Darbandi-Tehrani, K., Hermand, P., Carvalho, S., Dorgham, K., Couvineau, A., Lacapère, J.-J., Combadière, C., and Deterre, P. (2010). Subtle conformational changes between CX3CR1 genetic variants as revealed by resonance energy transfer assays. FASEB J. 24, 4585-4598.
31. De, A. (2011). The new era of biolumi-nescence resonance energy transfer technology. Curr. Pharm. Biotechnol. 12, 558-568.
32. De, A., Loening, A. M., and Gambhir, S. S. (2007). An improved biolu-minescence resonance energy transfer strategy for imaging intracellu-lar events in single cells and living subjects. Cancer Res. 67, 7175-7183.
33. De, A., Ray, P., Loening, A. M., and Gambhir,S. S. (2009). BRET3:ared-shifted bioluminescence resonance energy transfer (BRET)-based integrated platform for imaging protein-protein interactions from single live cells and living animals. FASEB J. 23, 2702-2709.
34. Degorce, F., Card, A., Soh, S., Trin-quet, E., Knapik, G. P., and Xie, B. (2009). HTRF: a technology tailored for drug discovery - a review of theoretical aspects and recent applications. Curr. Chem. Genomics 3, 22-32.
35. Dinh,D. T., Qian, H., Seeber, R., Lim, E., Pfleger,K.,Eidne,K.A.,and Thomas, W. G. (2005). Helix I of beta-arrestin is involved in postendocytic traffick-ingbutisnot required for membrane translocation, receptor binding, and internalization. Mol. Pharmacol. 67, 375-382.
36. Elster, L., Elling, C., and Heding, A. (2007). Bioluminescence resonance energy transfer as a screening assay: focus on partial and inverse ago-nism. J. Biomol. Screen 12, 41-49.
37. Fruhwirth, G. O., Fernandes, L. P., Weitsman, G., Patel, G., Kelleher, M.,Lawler, K., Brock, A., Poland, S. P., Matthews, D. R., Kéri, G., Barber, P. R., Vojnovic, B., Ameer-Beg, S. M., Coolen, A. C., Fraternali, F., and Ng, T. (2011). How Förster resonance energy transfer imaging improves the understanding of protein interaction networks in cancer biology. Chemphyschem 12, 442-461.
38. Galés, C., Van Durm, J. J. J., Schaak, S., Pontier, S., Percherancier, Y., Audet, M., Paris, H., and Bou-vier, M. (2006). Probing the activation-promoted structural rearrangements in preassembled receptor-G protein complexes. Nat. Struct. Mol. Biol. 13, 778-786.
39. Granier, S., Terrillon, S., Pascal, R., Déméné, H., Bouvier, M., Guillon, G., and Mendre, C. (2004). A cyclic peptide mimicking the third intra-cellular loop of the V2 vasopressin receptor inhibits signaling through its interaction with receptor dimer and G protein. J. Biol. Chem. 279, 50904-50914.
40. Guan, R., Feng, X., Wu, X., Zhang, M., Zhang, X., Hébert, T. E., and Segaloff, D. L. (2009). Biolumi-nescence resonance energy transfer studies reveal constitutive dimeriza-tion of the human lutropin receptor and a lack of correlation between receptor activation and the propensity for dimerization. J. Biol. Chem. 284, 7483-7494.
41. Hall, M. P., Unch, J., Binkowski, B. F., Valley, M. P., Butler, B. L., Wood, M. G., Otto, P., Zimmerman, K., Vidugiris, G., Machleidt, T., Robers, M. B., Benink, H. A., Eggers, C. T., Slater, M. R., Meisenheimer, P. L., Klaubert, D. H., Fan, F., Encell, L. P., and Wood, K. V. (2012). Engineered Luciferase Reporter from a Deep Sea Shrimp Utilizing a Novel Imidazopyrazinone Substrate. ACS Chem. Biol. PMID: 22894855. [Epub ahead of print].
42. Hamdan, F. F., Audet, M., Garneau, P., Pelletier, J., and Bouvier, M. (2005). High-throughput screening of G protein-coupled receptor antagonists using a bioluminescence resonance energy transfer 1-based beta-arrestin2 recruitment assay. J. Bio-mol. Screen 10, 463-475.
43. Hamdi, A., and Colas, P. (2012). Yeast two-hybrid methods and their applications in drug discovery. Trends Pharmacol. Sci. 33, 109-118.
44. Harikumar, K. G., Dong, M., Cheng, Z., Pinon, D. I., Lybrand, T. P., and Miller, L. J. (2006). Transmembrane segment peptides can disrupt chole-cystokinin receptor oligomerization without affecting receptor function. Biochemistry 45, 14706-14716.
45. Hickerson, R., Majumdar, Z. K., Bau-com, A., Clegg, R. M., and Noller, H. F. (2005). Measurement of internal movements within the 30S riboso-mal subunit using Förster resonance energy transfer. J. Mol. Biol. 354, 459-472.
46. Hu, K., Clément, J.-F., Abrahamyan, L., Strebel, K., Bouvier, M., Kleiman, L., and Mouland,A. J. (2005).A human immunodeficiency virus type 1 protease biosensor assay using biolumi-nescence resonance energy transfer. J. Virol. Methods 128, 93-103.
47. Issad, T., Boute, N., Boubekeur, S., and Lacasa, D. (2005). Interaction of PTPB with the insulin receptor precursor during its biosynthesis in the endoplasmic reticulum. Biochimie 87, 111-116.
48. Jaeger, S., and Aloy, P. (2012). From protein interaction networks to novel therapeutic strategies. IUBMB life. Available at: http:// www.ncbi.nlm.nih.gov/pubmed/ 22573601 (accessed May 18, 2012).
49. Jarry, M., Diallo, M., Lecointre, C., Desrues, L., Tokay, T., Chatenet, D., Leprince, J., Rossi, O., Vaudry, H., Tonon, M.-C., Prézeau, L., Castel, H., and Gandolfo, P. (2010). The vasoactive peptides urotensin II and urotensin II-related peptide regulate astrocyte activity through common and distinct mechanisms: involvement in cell proliferation. Biochem. J. 428, 113-124.
50. Kamal, M., Marquez, M., Vau-thier, V., Leloire, A., Froguel, P., Jockers, R., and Couturier, C. (2009). Improved donor/acceptor BRET couples for monitoring beta-arrestin recruitment to G protein-coupled receptors. Biotechnol. J. 4, 1337-1344.
51. Kang, J.-H., Tsai-Morris, C.-H., and Dufau, M. L. (2011). Complex formation and interactions between transcription factors essential for human prolactin receptor gene transcription. Mol. Cell. Biol. 31, 3208-3222.
52. Kim, G. B., and Kim, Y.-P. (2012). Analysis of protease activity using quantum dots and resonance energy transfer. Theranostics 2, 127-138.
53. Kim, S. B., Suzuki, H., Sato, M., and Tao, H. (2011). Superluminescent variants of marine luciferases for bioas-says. Anal. Chem. 83, 8732-8740.
54. Kimura, T., Hiraoka, K., Kasahara, N., and Logg, C. R. (2010). Optimization of enzyme-substrate pairing for bioluminescence imaging of gene transfer using Renilla and Gaussia luciferases.J. Gene Med. 12,528-537.
55. Kocan, M., and Pfleger, K. D. G. (2011). Study of GPCR-protein interactionsby BRET. Methods Mol. Biol. 746, 357-371.
56. Kocan, M., See, H. B., Seeber, R. M., Eidne, K. A., and Pfleger, K. D. G. (2008). Demonstration of improvements to the bioluminescence resonance energy transfer (BRET) technology for the monitoring of G protein-coupled receptors in live cells. J. Biomol. Screen 13, 888-898.
57. Krause, R., von Mering, C., Bork, P., and Dandekar, T. (2004). Shared components of protein complexes- versatile building blocks or biochemical artefacts? Bioessays 26, 1333-1343.
58. Kulahin, N., Grunnet, L. G., Lundh, M., Christensen, D. P., Jorgensen, R., Heding, A., Billestrup, N., Berezin, V., Bock, E., and Mandrup-Poulsen, T. (2011). Direct demonstration of NCAM cis-dimerization and inhibitory effect of palmitoylation using the BRET2 technique. FEBS Lett. 585, 58-64.
59. Kulahin, N., Sanni,S. J., Slaaby, R., Nøhr, J., Gammeltoft, S., Hansen, J. L., and Jorgensen, R. (2012). A BRET assay for monitoring insulin receptor interactions and ligand pharmacology. J. Recept. Signal Transduct. Res. 32, 57-64.
60. Laursen, L. S., and Oxvig, C. (2005). Real-time measurement in living cells of insulin-like growth factor activity using bioluminescence resonance energy transfer. Biochem. Pharmacol. 69, 1723-1732.
61. Lee, K. H., Lee, S., Lee, W. Y., Yang, H. W., and Heo, W. D. (2010). Visualizing dynamic interaction between calmodulin and calmodulin-related kinases via a monitoring method in live mammalian cells. Proc. Natl. Acad. Sci. U.S.A. 107, 3412-3417.
62. Li, F., Yu, J., Zhang, Z., Cui, Z., Wang, D., Wei, H., and Zhang, X.-E. (2012). Buffer enhanced biolumi-nescence resonance energy transfer sensor based on Gaussia luciferase for in vitro detection of protease. Anal. Chim. Acta 724, 104-110.
63. Lievens, S., Peelman, F., De Boss-cher, K., Lemmens, I., and Tav-ernier, J. (2011). MAPPIT: a protein interaction toolbox built on insights in cytokine receptor signaling. Cytokine Growth Factor Rev. 22, 321-329.
64. Loening, A. M., Fenn, T. D., Wu, A. M., and Gambhir, S. S. (2006). Consensus guided mutagenesis of Renilla luciferase yields enhanced stability and light output. Protein Eng. Des. Sel. 19, 391-400.
65. Lohse, M. J., Hein, P., Hoffmann, C., Nikolaev, V. O., Vilardaga, J.-P., andBünemann, M. (2008). Kinetics of G-protein-coupled receptor signals in intact cells. Br. J. Pharmacol. 153(Suppl. 1), S125-S132.
66. Lohse, M. J., Nuber, S., and Hoffmann, C. (2012). Fluores-cence/bioluminescence resonance energy transfer techniques to study G-protein-coupled receptor activation and signaling. Pharmacol. Rev. 64, 299-336.
67. Majumdar, Z. K., Hickerson, R., Noller, H. F., and Clegg, R. M. (2005). Measurements of internal distance changes of the 30S ribosome using FRET with multiple donor-acceptor pairs: quantitative spectro-scopic methods. J. Mol. Biol. 351, 1123-1145.
68. Markova, S. V., Burakova, L. P., and Vysotski, E. S. (2012). High-active truncated luciferase of copepod Metridia longa. Biochem. Biophys. Res. Commun. 417, 98-103.
69. Matthiesen, K., and Nielsen, J. (2011). Cyclic AMP control measured in two compartments in HEK293 cells: phosphodiesterase K(M) is more important than phosphodiesterase localization. PLoS ONE 6, e24392. doi:10.1371/journal.pone.0024392
70. Mazars, A., and Fåhraeus, R. (2010). Using BRET to study chemical compound-induced disruptions of the p53-HDM2 interactions in live cells. Biotechnol. J. 5, 377-384.
71. Mercier, J.-F., Salahpour, A., Angers, S., Breit, A., and Bouvier, M. (2002). Quantitative assessment of beta 1- and beta 2-adrenergic receptor homo- and heterodimeriza-tion by bioluminescence resonance energy transfer. J. Biol. Chem. 277, 44925-44931.
72. Michelini, E., Cevenini, L., Mezzanotte, L., Coppa, A., and Roda, A. (2010). Cell-based assays: fuelling drug discovery. Anal. Bioanal. Chem. 398, 227-238.
73. Michnick, S. W., Ear, P. H., Manderson, E. N., Remy, I., and Stefan, E. (2007). Universal strategies in research and drug discovery based on protein-fragment complementation assays. Nat. Rev. Drug Discov. 6, 569-582.
74. Milligan, G. (2004). Applications of bioluminescence- and fluorescence resonance energy transfer to drug discovery at G protein-coupled receptors. Eur. J. Pharm. Sci. 21, 397-405.
75. Molinari, P., Casella, I., and Costa, T. (2008). Functional complementation of high-efficiency resonance energy transfer: a new tool for the study of protein binding interactions in living cells. Biochem. J. 409, 251-261.
76. Morell, M., Ventura, S., and Avilés, F. X. (2009). Protein complementation assays: approaches for the in vivo analysis of protein interactions. FEBS Lett. 583, 1684-1691.
77. Mullick, A., Xu, Y., Warren, R., Koutroumanis, M., Guilbault, C., Broussau, S., Malenfant, F., Bourget, L., Lamoureux, L., Lo, R., Caron, A. W., Pilotte, A., and Massie, B. (2006). The cumate gene-switch: a system for regulated expression in mammalian cells. BMC Biotechnol. 6, 43. doi:10.1186/1472-6750-6-43
78. No, D., Yao, T. P., and Evans, R. M. (1996). Ecdysone-inducible gene expression in mammalian cells and transgenic mice. Proc. Natl. Acad. Sci. U.S.A. 93, 3346-3351.
79. Oka,T.,Takagi,H.,Tohya,Y.,Murakami, K., Takeda, N., Wakita, T., and Katayama, K. (2011). Bioluminescence technologies to detect calicivirus protease activity in cell-free system and in infected cells.Antiviral Res. 90, 9-16.
80. Otsuji, T., Okuda-Ashitaka, E., Kojima, S., Akiyama, H., Ito, S., and Ohmiya, Y. (2004). Monitoring for dynamic biological processing by intramolecular bioluminescence resonance energy transfer system using secreted luciferase. Anal. Biochem. 329, 230-237.
81. Otto-Duessel, M., Khankaldyyan, V., Gonzalez-Gomez, I., Jensen, M. C., Laug, W. E., and Rosol, M. (2006). In vivo testing of Renilla luciferase substrate analogs in an orthotopic murine model of human glioblastoma. Mol. Imaging 5, 57-64.
82. Percherancier, Y., Germain-Desprez, D., Galisson, F., Mascle, X. H., Dianoux, L., Estephan, P., Chelbi-Alix, M. K., and Aubry, M. (2009). Role of SUMO in RNF4-mediated promyelocytic leukemia protein (PML) degradation: sumoylation of PML and phospho-switch control of its SUMO binding domain dissected in living cells. J. Biol. Chem. 284, 16595-16608.
83. Pfleger, K. D. G., Dalrymple, M. B., Dromey, J. R., and Eidne, K. A. (2007). Monitoring interactions between G-protein-coupled receptors and beta-arrestins. Biochem. Soc. Trans. 35, 764-766.
84. Pfleger, K. D. G., Dromey, J. R., Dal-rymple, M. B., Lim, E. M. L., Thomas, W. G., and Eidne, K. A. (2006). Extended bioluminescence resonance energy transfer (eBRET) for monitoring prolonged protein-protein interactions in live cells. Cell. Signal. 18, 1664-1670.
85. Pfleger,K.D.G.,and Eidne,K.A. (2003). New technologies: bioluminescenceresonance energy transfer (BRET) for the detection of real time interactions involving G-protein coupled receptors. Pituitary 6, 141-151.
86. Pfleger, K. D. G., and Eidne, K. A. (2006). Illuminating insights into protein-protein interactions using bioluminescence resonance energy transfer (BRET). Nat. Methods 3, 165-174.
87. Py, B., Basmaciogullari, S., Bouchet, J., Zarka, M., Moura, I. C., Benhamou, M., Monteiro, R. C., Hocini, H., Madrid, R., and Benichou,S. (2009). The phospholipid scramblases 1 and 4 are cellular receptors for the secretory leukocyte protease inhibitor and interact with CD4 at the plasma membrane. PLoS ONE 4, e5006. doi:10.1371/journal.pone.0005006
88. Qi, Q., He, K., Liu, X., Pham, C., Meyerkord, C., Fu, H., and Ye, K. (2012). Disrupting the PIKE-A/Akt interaction inhibits glioblas-toma cell survival, migration, invasion and colony formation. Oncogene. Available at: http:// www.ncbi.nlm.nih.gov/pubmed/ 22450747 (accessed May 25, 2012).
89. Quiñones, G. A., Miller, S. C., Bhat-tacharyya, S., Sobek,D., and Stephan, J.-P. (2012). Ultrasensitive detection of cellular protein interactions using bioluminescence resonance energy transfer quantum dot-based nanoprobes. J. Cell. Biochem. 113, 2397-2405.
90. Ramsay, D., Kellett, E., McVey, M., Rees, S., and Milligan, G. (2002). Homo- and hetero-oligomeric interactions between G-protein-coupled receptors in living cells monitored by two variants of biolumines-cence resonance energy transfer (BRET): hetero-oligomers between receptor subtypes form more efficiently than between less closely related sequences. Biochem. J. 365, 429-440.
91. Schelshorn, D., Joly, F., Mutel, S., Hampe, C., Breton, B., Mutel, V., and Lütjens, R. (2012). Lateral allosterism in the glucagon receptor family: glucagon-like peptide 1 induces G-protein-coupled receptor heteromer formation. Mol. Pharmacol. 81, 309-318.
92. See, H. B., Seeber, R. M., Kocan, M., Eidne, K. A., and Pfleger, K. D. G. (2011). Application of G protein-coupled receptor-heteromer identification technology to monitor β-arrestin recruitment to G protein-coupled receptor heteromers. Assay Drug Dev. Technol. 9, 21-30.
93. Shockett, P. E., and Schatz, D. G. (1996). Diverse strategies for tetracycline-regulated inducible gene expression.Proc. Natl. Acad. Sci. U.S.A. 93, 5173-5176.
94. Smith, D. S., and Eremin, S. A. (2008). Fluorescence polarization immunoassays and related methods for simple, high-throughput screening of small molecules. Anal. Bioanal. Chem. 391, 1499-1507.
95. So, M.-K., Xu, C., Loening, A. M., Gambhir, S. S., and Rao, J. (2006). Self-illuminating quantum dot conjugates for in vivo imaging. Nat. Biotechnol. 24, 339-343.
96. Soenen, S. J., Demeester, J., De Smedt, S. C., and Braeckmans, K. (2012). The cytotoxic effects of polymer-coated quantum dots and restrictions for live cell applications. Biomaterials 33, 4882-4888.
97. Stryer, L., and Haugland, R. P. (1967). Energy transfer: a spectroscopic ruler. Proc. Natl. Acad. Sci. U.S.A. 58, 719.
98. Subramanian, C., Xu, Y., Johnson, C. H., and von Arnim, A. G. (2004). In vivo detection of protein-protein interaction in plant cells using BRET. Methods Mol. Biol. 284, 271-286.
99. Sun, Y., Chen, X., and Xiao, D. (2007). Tetracycline-inducible expression systems: new strategies and practices in the transgenic mouse modeling. Acta Biochim. Biophys. Sin. (Shanghai) 39, 235-246.
100. Takakura, H., Kojima, R., Urano, Y., Terai, T., Hanaoka, K., and Nagano, T. (2011). Aminoluciferins as functional bioluminogenic substrates of firefly luciferase. Chem. Asian J. 6, 1800-1810.
101. Takakura, H., Sasakura, K., Ueno, T., Urano, Y., Terai, T., Hanaoka, K., Tsuboi, T., and Nagano, T. (2010). Development of luciferin analoguesbearing an amino group and their application as BRET donors. Chem. Asian J. 5, 2053-2061.
102. Takenaka, Y., Masuda, H., Yamaguchi, A., Nishikawa, S., Shigeri,Y.,Yoshida, Y., and Mizuno, H. (2008). Two forms of secreted and thermostable luciferases from the marine copepod crustacean, Metridia pacifica. Gene 425, 28-35.
103. Tannous, B. A., Kim, D.-E., Fernandez, J. L., Weissleder, R., and Breakefield, X. O. (2005). Codon-optimized Gaus-sia luciferase cDNA for mammalian gene expression in culture and in vivo. Mol. Ther. 11, 435-443.
104. Tavernier, J., Eyckerman, S., Lem-mens, I., Van der Heyden, J., Van-dekerckhove, J., and Van Ostade, X. (2002). MAPPIT: a cytokine receptor-based two-hybrid method in mammalian cells. Clin. Exp. Allergy 32, 1397-1404.
105. Terrillon, S., Durroux, T., Mouil-lac, B., Breit, A., Ayoub, M. A., Taulan, M., Jockers, R., Barberis, C., and Bouvier, M. (2003). Oxy-tocin and vasopressin V1a and V2 receptors form constitutive homo- and heterodimers during biosynthesis. Mol. Endocrinol. 17, 677-691.
106. Ventura, S. (2011). Bimolecular fluorescence complementation: illuminating cellular protein interactions. Curr. Mol. Med. 11, 582-598.
107. Vilardaga, J.-P., Bünemann, M., Krasel, C., Castro, M., and Lohse, M. J. (2003). Measurement of the millisecond activation switch of G protein-coupled receptors in living cells. Nat. Biotechnol. 21, 807-812.
108. Vizoso Pinto, M. G., Pothineni, V. R., Haase, R., Woidy, M., Lotz-Havla,A. S., Gersting, S. W., Muntau, A. C., Haas, J., Sommer, M., Arvin, A. M., and Baiker, A. (2011). Varicella zoster virus ORF25 gene product: an essential hub protein linking encap-sidation proteins and the nuclear egress complex. J. Proteome Res. 10, 5374-5382.
109. Vrecl, M., Jorgensen, R., Pogacnik, A., and Heding, A. (2004). Development of a BRET2 screening assay using beta-arrestin 2 mutants. J. Bio-mol. Screen 9, 322-333.
110. Welsh, J. P., Patel, K. G., Man-thiram, K., and Swartz, J. R. (2009). Multiply mutated Gaussia luciferases provide prolonged and intense bioluminescence. Biochem. Biophys. Res. Commun. 389, 563-568.
111. Weng, J., and Ren, J. (2006). Luminescent quantum dots: a very attractive and promising tool in bio-medicine. Curr. Med. Chem. 13, 897-909.
112. Xia, Z., Xing, Y., So, M.-K., Koh, A. L., Sinclair, R., and Rao, J. (2008). Multiplex detection of protease activity with quantum dot nanosensors prepared by intein-mediated specific bioconjugation. Anal. Chem. 80, 8649-8655.
113. Xiao, Y., Beilstein, M. A., Wang, M., Purintrapiban, J., and Forsberg, N. E. (2003). Development of a ponas-terone A-inducible gene expression system for application in cultured skeletal muscle cells. Int. J. Biochem. Cell Biol. 35, 79-85.
114. Xu, Y., Piston, D. W., and Johnson, C. H. (1999). A bioluminescence resonance energy transfer (BRET) system: application to interacting circa-dian clock proteins. Proc. Natl. Acad. Sci. U.S.A. 96, 151-156.
115. Yamakawa, Y., Ueda, H., Kitayama, A., and Nagamune, T. (2002). Rapid homogeneous immunoassay of pep-tides based on bioluminescence resonance energy transfer from firefly luciferase. J. Biosci. Bioeng. 93, 537-542.
116. Zhao, H., Doyle, T. C., Wong, R. J., Cao, Y., Stevenson, D. K., Piwnica-Worms, D., and Contag, C. H. (2004). Characterization of coelen-terazine analogs for measurements of Renilla luciferase activity in live cells and living animals. Mol. Imaging 3, 43-54.