237
7. Hubbard SR, Miller WT (2007) Receptor tyrosine kinases: mechanisms of activation and signaling. Curr Opin Cell Biol 19:117–123.
doi:10.1016/j.ceb.2007.02.010
8. Petschnigg J, Groisman B, Kotlyar M, Taipale
M, Zheng Y, Kurat CF, Sayad A, Sierra JR,
Usaj MM, Snider J, Nachman A, Krykbaeva I,
Tsao M-S, Moffat J, Pawson T, Lindquist S,
Jurisica I, Stagljar I (2014) The mammalianmembrane two-hybrid assay (MaMTH) for
probing membrane-protein interactions in
human cells. Nat Methods. doi:10.1038/
nmeth.2895
9. Wehr M, Reinecke L, Botvinnik A, Rossner M
(2008) Analysis of transient phosphorylationdependent protein-protein interactions in living
mammalian cells using split-TEV. BMC Biotechnol 8:55. doi:10.1186/1472-6750-8-55
10. Antczak C, Bermingham A, Calder P, Malkov
D, Song K, Fetter J, Djaballah H (2012)
Domain-based biosensor assay to screen for
epidermal growth factor receptor modulators
in live cells. Assay Drug Dev Technol 10:24–
36. doi:10.1089/adt.2011.423
11. Dorsam RT, Gutkind JS (2007) G-proteincoupled receptors and cancer. Nat Rev Cancer
7:79–94. doi:10.1038/nrc2069
12. Lagerström MC, Schiöth HB (2008) Structural
diversity of G protein-coupled receptors and
significance for drug discovery. Nat Rev Drug
Discov 7:339–357. doi:10.1038/nrd2518
13. Kohout TA, Lefkowitz RJ (2003) Regulation
of G protein-coupled receptor kinases and
arrestins during receptor desensitization. Mol
Pharmacol 63:9–18
14. MacDonald ML, Lamerdin J, Owens S, Keon
BH, Bilter GK, Shang Z, Huang Z, Yu H, Dias
J, Minami T, Michnick SW, Westwick JK
(2006) Identifying off-target effects and hidden
phenotypes of drugs in human cells. Nat Chem
Biol 2:329–337. doi:10.1038/nchembio790
15. Djannatian MS, Galinski S, Fischer TM,
Rossner MJ (2011) Studying G proteincoupled receptor activation using split-tobacco
etch virus assays. Anal Biochem 412:141–152.
doi:16/j.ab.2011.01.042
16. Barnea G, Strapps W, Herrada G, Berman Y,
Ong J, Kloss B, Axel R, Lee KJ (2008) The
genetic design of signaling cascades to record
receptor activation. Proc Natl Acad Sci 105:64–
69. doi:10.1073/pnas.0710487105
17. Misawa N, Kafi AKM, Hattori M, Miura K,
Masuda K, Ozawa T (2010) Rapid and highsensitivity cell-based assays of protein-protein
interactions using split click beetle luciferase
complementation: an approach to the study of
G-protein-coupled receptors. Anal Chem
82:2552–2560. doi:10.1021/ac100104q
18. Ghosh I, Hamilton AD, Regan L (2000)
Antiparallel leucine zipper-directed protein
reassembly: application to the green fluorescent
protein. J Am Chem Soc 122:5658–5659.
doi:10.1021/ja994421w
19. Hu C-D, Chinenov Y, Kerppola TK (2002)
Visualization of interactions among bZIP and
Rel family proteins in living cells using bimolecular fluorescence complementation. Mol
Cell 9:789–798
20. Shyu YJ, Liu H, Deng X, Hu C-D (2006)
Identification of new fluorescent protein fragments for bimolecular fluorescence complementation analysis under physiological
conditions. BioTechniques 40:61–66
21. Luker KE, Smith MCP, Luker GD, Gammon
ST, Piwnica-Worms H, Piwnica-Worms D
(2004) Kinetics of regulated protein–protein
interactions revealed with firefly luciferase complementation imaging in cells and living animals. PNAS 101:12288–12293. doi:10.1073/
pnas.0404041101
22. Paulmurugan R, Umezawa Y, Gambhir SS
(2002) Noninvasive imaging of protein- protein
interactions in living subjects by using reporter
protein complementation and reconstitution
strategies. Proc Natl Acad Sci U S A 99:15608–
15613. doi:10.1073/pnas.242594299
23. Kaihara A, Kawai Y, Sato M, Ozawa T,
Umezawa Y (2003) Locating a protein-protein interaction in living cells via split Renilla
luciferase complementation. Anal Chem 75:
4176–4181
24. Paulmurugan R, Gambhir SS (2003)
Monitoring protein-protein interactions using
split synthetic renilla luciferase proteinfragment- assisted complementation. Anal
Chem 75:1584–1589
25. Remy I, Michnick SW (2006) A highly sensitive protein-protein interaction assay based on
Gaussia luciferase. Nat Methods 3:977–979.
doi:10.1038/nmeth979
26. Kim SB, Otani Y, Umezawa Y, Tao H (2007)
Bioluminescent indicator for determining
protein- protein interactions using intramolecular complementation of split click beetle luciferase. Anal Chem 79:4820–4826. doi:10.1021/
ac0621571
27. Hida N, Awais M, Takeuchi M, Ueno N,
Tashiro M, Takagi C, Singh T, Hayashi M,
Ohmiya Y, Ozawa T (2009) High-sensitivity
real-time imaging of dual protein-protein interactions in living subjects using multicolor luciferases. PLoS ONE 4:e5868. doi:10.1371/
journal.pone.0005868
28. Galarneau A, Primeau M, Trudeau L-E,
Michnick SW (2002) Beta-lactamase protein
fragment complementation assays as in vivo and
Characterising Dynamic PPIs Using Split TEV
7. Hubbard SR, Miller WT (2007) Receptor tyrosine kinases: mechanisms of activation and signaling. Curr Opin Cell Biol 19:117–123.
doi:10.1016/j.ceb.2007.02.010
8. Petschnigg J, Groisman B, Kotlyar M, Taipale
M, Zheng Y, Kurat CF, Sayad A, Sierra JR,
Usaj MM, Snider J, Nachman A, Krykbaeva I,
Tsao M-S, Moffat J, Pawson T, Lindquist S,
Jurisica I, Stagljar I (2014) The mammalianmembrane two-hybrid assay (MaMTH) for
probing membrane-protein interactions in
human cells. Nat Methods. doi:10.1038/
nmeth.2895
9. Wehr M, Reinecke L, Botvinnik A, Rossner M
(2008) Analysis of transient phosphorylationdependent protein-protein interactions in living
mammalian cells using split-TEV. BMC Biotechnol 8:55. doi:10.1186/1472-6750-8-55
10. Antczak C, Bermingham A, Calder P, Malkov
D, Song K, Fetter J, Djaballah H (2012)
Domain-based biosensor assay to screen for
epidermal growth factor receptor modulators
in live cells. Assay Drug Dev Technol 10:24–
36. doi:10.1089/adt.2011.423
11. Dorsam RT, Gutkind JS (2007) G-proteincoupled receptors and cancer. Nat Rev Cancer
7:79–94. doi:10.1038/nrc2069
12. Lagerström MC, Schiöth HB (2008) Structural
diversity of G protein-coupled receptors and
significance for drug discovery. Nat Rev Drug
Discov 7:339–357. doi:10.1038/nrd2518
13. Kohout TA, Lefkowitz RJ (2003) Regulation
of G protein-coupled receptor kinases and
arrestins during receptor desensitization. Mol
Pharmacol 63:9–18
14. MacDonald ML, Lamerdin J, Owens S, Keon
BH, Bilter GK, Shang Z, Huang Z, Yu H, Dias
J, Minami T, Michnick SW, Westwick JK
(2006) Identifying off-target effects and hidden
phenotypes of drugs in human cells. Nat Chem
Biol 2:329–337. doi:10.1038/nchembio790
15. Djannatian MS, Galinski S, Fischer TM,
Rossner MJ (2011) Studying G proteincoupled receptor activation using split-tobacco
etch virus assays. Anal Biochem 412:141–152.
doi:16/j.ab.2011.01.042
16. Barnea G, Strapps W, Herrada G, Berman Y,
Ong J, Kloss B, Axel R, Lee KJ (2008) The
genetic design of signaling cascades to record
receptor activation. Proc Natl Acad Sci 105:64–
69. doi:10.1073/pnas.0710487105
17. Misawa N, Kafi AKM, Hattori M, Miura K,
Masuda K, Ozawa T (2010) Rapid and highsensitivity cell-based assays of protein-protein
interactions using split click beetle luciferase
complementation: an approach to the study of
G-protein-coupled receptors. Anal Chem
82:2552–2560. doi:10.1021/ac100104q
18. Ghosh I, Hamilton AD, Regan L (2000)
Antiparallel leucine zipper-directed protein
reassembly: application to the green fluorescent
protein. J Am Chem Soc 122:5658–5659.
doi:10.1021/ja994421w
19. Hu C-D, Chinenov Y, Kerppola TK (2002)
Visualization of interactions among bZIP and
Rel family proteins in living cells using bimolecular fluorescence complementation. Mol
Cell 9:789–798
20. Shyu YJ, Liu H, Deng X, Hu C-D (2006)
Identification of new fluorescent protein fragments for bimolecular fluorescence complementation analysis under physiological
conditions. BioTechniques 40:61–66
21. Luker KE, Smith MCP, Luker GD, Gammon
ST, Piwnica-Worms H, Piwnica-Worms D
(2004) Kinetics of regulated protein–protein
interactions revealed with firefly luciferase complementation imaging in cells and living animals. PNAS 101:12288–12293. doi:10.1073/
pnas.0404041101
22. Paulmurugan R, Umezawa Y, Gambhir SS
(2002) Noninvasive imaging of protein- protein
interactions in living subjects by using reporter
protein complementation and reconstitution
strategies. Proc Natl Acad Sci U S A 99:15608–
15613. doi:10.1073/pnas.242594299
23. Kaihara A, Kawai Y, Sato M, Ozawa T,
Umezawa Y (2003) Locating a protein-protein interaction in living cells via split Renilla
luciferase complementation. Anal Chem 75:
4176–4181
24. Paulmurugan R, Gambhir SS (2003)
Monitoring protein-protein interactions using
split synthetic renilla luciferase proteinfragment- assisted complementation. Anal
Chem 75:1584–1589
25. Remy I, Michnick SW (2006) A highly sensitive protein-protein interaction assay based on
Gaussia luciferase. Nat Methods 3:977–979.
doi:10.1038/nmeth979
26. Kim SB, Otani Y, Umezawa Y, Tao H (2007)
Bioluminescent indicator for determining
protein- protein interactions using intramolecular complementation of split click beetle luciferase. Anal Chem 79:4820–4826. doi:10.1021/
ac0621571
27. Hida N, Awais M, Takeuchi M, Ueno N,
Tashiro M, Takagi C, Singh T, Hayashi M,
Ohmiya Y, Ozawa T (2009) High-sensitivity
real-time imaging of dual protein-protein interactions in living subjects using multicolor luciferases. PLoS ONE 4:e5868. doi:10.1371/
journal.pone.0005868
28. Galarneau A, Primeau M, Trudeau L-E,
Michnick SW (2002) Beta-lactamase protein
fragment complementation assays as in vivo and
Characterising Dynamic PPIs Using Split TEV