Noninvasive imaging of protein-protein interactions in living animals

Gary D. Luker, Vijay Sharma, Christina M. Pica, Julie L. Dahlheimer, Wei Li, Joseph Ochesky, Christine E. Ryan, Helen Piwnica-Worms, David Piwnica-Worms

Research output: Contribution to journalArticle

152 Scopus citations

Abstract

Protein-protein interactions control transcription, cell division, and cell proliferation as well as mediate signal transduction, oncogenic transformation, and regulation of cell death. Although a variety of methods have been used to investigate protein interactions in vitro and in cultured cells, none can analyze these interactions in intact, living animals. To enable noninvasive molecular imaging of protein-protein interactions in vivo by positron-emission tomography and fluorescence imaging, we engineered a fusion reporter gene comprising a mutant herpes simplex virus 1 thymidine kinase and green fluorescent protein for readout of a tetracycline-inducible, two-hybrid system in vivo. By using micro-positron-emission tomography, interactions between p53 tumor suppressor and the large T antigen of simian virus 40 were visualized in tumor xenografts of HeLa cells stably transfected with the imaging constructs. Imaging protein-binding partners in vivo will enable functional proteomics in whole animals and provide a tool for screening compounds targeted to specific protein-protein interactions in living animals.

Original languageEnglish
Pages (from-to)6961-6966
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number10
DOIs
StatePublished - May 14 2002

Fingerprint Dive into the research topics of 'Noninvasive imaging of protein-protein interactions in living animals'. Together they form a unique fingerprint.

  • Cite this

    Luker, G. D., Sharma, V., Pica, C. M., Dahlheimer, J. L., Li, W., Ochesky, J., Ryan, C. E., Piwnica-Worms, H., & Piwnica-Worms, D. (2002). Noninvasive imaging of protein-protein interactions in living animals. Proceedings of the National Academy of Sciences of the United States of America, 99(10), 6961-6966. https://doi.org/10.1073/pnas.092022399