DOI: 10.1073/pnas.0710487105. The genetic design of signaling cascades to record receptor activation

The genetic design of signaling cascades to record receptor activation

10.1073/pnas.0710487105

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

We have developed an experimental strategy to monitor protein interactions in a cell with a high degree of selectivity and sensitivity. A transcription factor is tethered to a membrane-bound receptor with a linker that contains a cleavage site for a specific protease. Activation of the receptor recruits a signaling protein fused to the protease that then cleaves and releases the transcription factor to activate reporter genes in the nucleus. This strategy converts a transient interaction into a stable and amplifiable reporter gene signal to record the activation of a receptor without interference from endogenous signaling pathways. We have developed this assay for three classes of receptors: G protein-coupled receptors, receptor tyrosine kinases, and steroid hormone receptors. Finally, we use the assay to identify a ligand for the orphan receptor GPR1, suggesting a role for this receptor in the regulation of inflammation.

Bibliography

Barnea, G., Strapps, W., Herrada, G., Berman, Y., Ong, J., Kloss, B., Axel, R., & Lee, K. J. (2008). The genetic design of signaling cascades to record receptor activation. Proceedings of the National Academy of Sciences, 105(1), 64â69.

Authors 8

Gilad Barnea (first)
Walter Strapps (additional)
Gilles Herrada (additional)
Yemiliya Berman (additional)
Jane Ong (additional)
Brian Kloss (additional)
Richard Axel (additional)
Kevin J. Lee (additional)

References 27 Referenced 609

Dates

Type	When
Created	17 years, 8 months ago (Dec. 28, 2007, 8:41 p.m.)
Deposited	2 years, 4 months ago (April 26, 2023, 2:09 p.m.)
Indexed	2 weeks, 6 days ago (Aug. 12, 2025, 5:26 p.m.)
Issued	17 years, 7 months ago (Jan. 8, 2008)
Published	17 years, 7 months ago (Jan. 8, 2008)
Published Online	17 years, 7 months ago (Jan. 8, 2008)
Published Print	17 years, 7 months ago (Jan. 8, 2008)

Funders 0

None

BibTeX

@article{Barnea_2008, title={The genetic design of signaling cascades to record receptor activation}, volume={105}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0710487105}, DOI={10.1073/pnas.0710487105}, number={1}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Barnea, Gilad and Strapps, Walter and Herrada, Gilles and Berman, Yemiliya and Ong, Jane and Kloss, Brian and Axel, Richard and Lee, Kevin J.}, year={2008}, month=jan, pages={64–69} }

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