Imaging Protein-Protein Interactions in Whole Cells and Living Animals

  • D. Piwnica-Worms
  • K. E. Luker
Part of the Ernst Schering Research Foundation Workshop book series (SCHERING FOUND, volume 49)

2.4 Conclusions

These studies demonstrate that noninvasive molecular imaging of protein-protein interactions may enable investigators to determine how intrinsic binding specificities of proteins are regulated in a wide variety of normal and pathophysiologic conditions. These tools provide a platform for detection of regulated and small molecule-induced protein-protein interactions in intact cells and living animals and should enable a wide range of novel applications in biomedi-cine, drug discovery, chemical genetics, and proteomics research.


Living Animal Hybrid Protein Fragment Complementation Sharma Versus Tron Emission Tomography 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Chen J, Zheng XF, Brown EJ, Schreiber SL (1995) Identification of an 11-kDa FKBP 12-rapamycin-binding domain within the 289-kDa FKBP12-ra-pamycin-associated protein and characterization of a critical serine residue. Proc Natl Acad Sci USA 92:4947–4951PubMedCrossRefGoogle Scholar
  2. Darnell JE Jr (2002) Transcription factors as targets for cancer therapy. Nat Rev Cancer 2:740–749PubMedCrossRefGoogle Scholar
  3. Fields S, Song O (1989) A novel genetic system to detect protein-protein interaction. Nature 340:245–246PubMedCrossRefGoogle Scholar
  4. Galarneau A, Primeau M, Trudeau LE, Michnick S (2002) β-Lactamase protein fragment complementation assays as in vivo and in vitro sensors of protein-protein interactions. Nat Biotechnol 20:619–622PubMedCrossRefGoogle Scholar
  5. Heldin C (2001) Signal transduction: multiple pathways, multiple options for therapy. Stem Cells 19:295–303PubMedCrossRefGoogle Scholar
  6. Luker K, Piwnica-Worms D (2004) Optimizing luciferase protein fragment complementation for bioluminescent imaging of protein-protein interactions in live cells and animals. Methods Enzymology 385:349–360CrossRefGoogle Scholar
  7. Luker G, Sharma V, Pica C, Dahlheimer J, Li W, Ochesky J, Ryan C, Piwnica-Worms H, Piwnica-Worms D (2002) Noninvasive imaging of protein-protein interactions in living animals. Proc Natl Acad Sci USA 99:6961–6966PubMedCrossRefGoogle Scholar
  8. Luker G, Sharma V, Pica C, Prior J, Li W, Piwnica-Worms D (2003 a) Molecular imaging of protein-protein Interactions: controlled expression of p53 and large T antigen fusion proteins in vivo. Cancer Res 63:1780–1788PubMedGoogle Scholar
  9. Luker G, Sharma V, Piwnica-Worms D (2003 b) Visualizing protein-protein interactions in living animals. Methods 29:110–122PubMedCrossRefGoogle Scholar
  10. Luker G, Sharma V, Piwnica-Worms D (2003 c) Noninvasive imaging of protein-protein interactions in living animals. In Conn PM (ed) Handbook of proteomic methods. Humana Press, Inc., Totowa, NJ, pp 283–298CrossRefGoogle Scholar
  11. Ogawa H, Ishiguro S, Gaubatz S, Livingston D, Nakatani Y (2002) A complex with chromatin modifiers that occupies E2F-and Myc-responsive genes in GO cells. Science 296:1132–1136PubMedCrossRefGoogle Scholar
  12. Ostermeier M, Nixon A, Shim J, Benkovic S (1999) Combinatorial protein engineering by incremental truncation. Proc Natl Acad Sci USA 96: 3562–3567PubMedCrossRefGoogle Scholar
  13. Ozawa T, Kaihara A, Sato M, Tachihara K, Umezawa Y (2001) Split luciferase as an optical probe for detecting protein-protein interactions in mammalian cells based on protein splicing. Anal Chem 73:2516–2521PubMedCrossRefGoogle Scholar
  14. Paulmurugan R, Gambhir S (2003) Monitoring protein-protein interactions using split synthetic Renilla luciferase protein-fragment-assisted complementation. Anal Chem 75:1584–1589PubMedCrossRefGoogle Scholar
  15. 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 USA 99:15608–15613PubMedCrossRefGoogle Scholar
  16. Ray P, Pimenta H, Paulmurugan R, Berger F, Phelps M, Iyer M, Gambhir S (2002) Noninvasive quantitative imaging of protein-protein interactions in living subjects. Proc Natl Acad Sci USA 99:2105–3110CrossRefGoogle Scholar
  17. Remy I, Michnick S (1999) Clonal selection and in vivo quantitation of protein interactions with protein-fragment complementation assays. Proc Natl Acad Sci USA 96:5394–5399PubMedCrossRefGoogle Scholar
  18. Remy I, Wilson I, Michnick S (1999) Erythropoietin receptor activation by a ligand-induced conformation change. Science 283:990–993PubMedCrossRefGoogle Scholar
  19. Rossi F, Charlton C, Blau H (1997) Monitoring protein-protein interactions in intact eukaryotic cells by β-galactosidase complementation. Proc Natl Acad Sci USA 94:8405–8410PubMedCrossRefGoogle Scholar
  20. Rossi F, Blakely B, Blau H (2000) Interaction blues: protein interactions monitored in live mammalian cells by β-galactosidase complementation. Trends Cell Bid 10:119–122CrossRefGoogle Scholar
  21. Stark G, Kerr I, Williams B, Silverman R, Schreiber R (1998) How cells respond to interferons. Annu Rev Biochem 67:227–264PubMedCrossRefGoogle Scholar
  22. Toby G, Golemis E (2001) Using the yeast interaction trap and other two-hybrid-based approaches to study protein-protein interactions. Methods 24:201–217PubMedCrossRefGoogle Scholar
  23. von Mering C, Krause R, Snel B, Cornell M, Oliver S, Fields S, Bork P (2002) Comparative assessment of large-scale sets of protein-protein interactions. Nature 471:399–403CrossRefGoogle Scholar
  24. Wehrman T, Kleaveland B, Her JH, Balint RF, Blau HM (2002) Protein-protein interactions monitored in mammalian cells via complementation of β-lactamase enzyme fragments. Proc Natl Acad Sci USA 99:3469–3474PubMedCrossRefGoogle Scholar
  25. Zhang H, Hu G, Wang H, Sciavolino P, Her N, Shen M, Abate-Shen C (1997) Heterodimerization of Msx and Dlx homeoproteins results in functional antagonism. Mol Cell Biol 17:2920–2932PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2005

Authors and Affiliations

  • D. Piwnica-Worms
    • 1
  • K. E. Luker
    • 2
  1. 1.Washington University School of Medicine Molecular Imaging CenterSt. LouisUSA
  2. 2.Molecular Imaging Center, Mallinckrodt Institute of Radiology, and Department of Molecular Biology and PharmacologyWashington University Medical SchoolSt. LouisUSA

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