NDLI: Imaging chemokine receptor dimerization with firefly luciferase complementation

Content Provider	PubMed Central
Author	Luker, Kathryn E. Gupta, Mudit Luker, Gary D.
Copyright Year	2009
Abstract	Seven-transmembrane (G-protein coupled) receptors are key regulators of normal physiology and a large number of diseases, and this family of receptors is the target for almost half of all drugs. Cell culture models suggest that homodimerization and heterodimerization of 7-transmembrane receptors regulate processes including specificity of ligand binding and activation of downstream signaling pathways, making receptor dimerization a critical determinant of receptor biology and a promising new therapeutic target. To monitor receptor dimerization in cell-based assays and living animals, we developed a protein fragment complementation assay based on firefly luciferase to investigate dimerization of chemokine receptors CXCR4 and CXCR7, two 7-transmembrane receptors with central functions in normal development, cancer, and other diseases. Treatment with chemokine ligands and pharmacologic agents produced time- and dose-dependent changes in reporter signal. Chemokines regulated reporter bioluminescence for CXCR4 or CXCR7 homodimers without affecting signals from receptor heterodimers. In a tumor xenograft model of breast cancer, we used bioluminescence imaging to measure changes in receptor homodimerization in response to pharmacologic agents. This technology should be valuable for analyzing function and therapeutic modulation of receptor dimerization in intact cells and living mice.—Luker, K. E., Gupta, M., Luker, G. D. Imaging chemokine receptor dimerization with firefly luciferase complementation.
Related Links	http://dx.doi.org/10.1096/fj.08-116749
Starting Page	823
File Format	PDF
ISSN	15306860
e-ISSN	15306860
Journal	The FASEB Journal
Issue Number	3
Volume Number	23
Language	English
Publisher	The Federation of American Societies for Experimental Biology
Publisher Date	2009-03-01
Access Restriction	Open
Rights Holder	The Federation of American Societies for Experimental Biology
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics Medicine Molecular Biology Biochemistry Biotechnology

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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