Label-free impedance responses of endogenous and synthetic chemokine receptor CXCR3 agonists correlate with Gi-protein pathway activation

Biochemical and Biophysical Research Communications
Anne O WattsRob Leurs

Abstract

The chemokine receptor CXCR3 is a G-protein-coupled receptor that signals through the Gα(i) class of heterotrimeric G-proteins. CXCR3 is highly expressed on activated T cells and has been proposed to be a therapeutic target in autoimmune disease. CXCR3 is activated by the chemokines CXCL9, CXCL10 and CXCL11. CXCR3 signaling properties in response to CXCL10, CXCL11 and the synthetic agonist VUF10661 have previously been evaluated using conventional endpoint assays. In the present study, label-free impedance measurements were used to characterize holistic responses of CXCR3-expressing cells to stimulation with chemokines and VUF10661 in real time and to compare these responses with both G-protein and non-G-protein (β-arrestin2) mediated responses. Differences in response kinetics were apparent between the chemokines and VUF10661. Moreover, CXCR3-independent effects could be distinguished from CXCR3-specific responses with the use of the selective CXCR3 antagonist NBI-74330 and the Gα(i) inhibitor pertussis toxin. By comparing the various responses, we observed that CXCL9 is a biased CXCR3 agonist, stimulating solely G-protein-dependent pathways. Moreover, CXCR3-mediated changes in cellular impedance correlated with G-protein sign...Continue Reading

References

May 20, 2004·The Journal of Biological Chemistry·Richard A ColvinAndrew D Luster
May 29, 2004·Naunyn-Schmiedeberg's Archives of Pharmacology·Elizabeth M RosethorneSteven J Charlton
Mar 12, 2005·The Journal of Pharmacology and Experimental Therapeutics·Christopher E HeiseDavid G Alleva
Aug 26, 2006·Biochemical and Biophysical Research Communications·Ilana L StrokeMaria L Webb
Feb 7, 2008·Cardiovascular Research·Maria Luisa BalestrieriClaudio Napoli
Feb 13, 2009·Journal of Biomolecular Screening·Matthew F Peters, Clay W Scott
Jun 18, 2009·Combinatorial Chemistry & High Throughput Screening·R P McGuinnessP H Lee
Jul 18, 2009·Nature Reviews. Drug Discovery·Terry P Kenakin
Dec 30, 2009·Cellular Immunology·Jiang-Hong GongRobert E W Hancock
Mar 6, 2010·The American Journal of Pathology·Cecelia C YatesAlan Wells
Aug 11, 2011·Biochemical and Biophysical Research Communications·M KammermannC Hertel

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Citations

May 13, 2014·Analytical and Bioanalytical Chemistry·Peter FechnerJulia Widmaier
Apr 1, 2014·Trends in Immunology·Annelien J M ZweemerAdriaan P IJzerman
Nov 5, 2015·Journal of Medicinal Chemistry·Stephen P Andrews, Rhona J Cox
Apr 20, 2017·Journal of Molecular Endocrinology·J Jason CollierSusan J Burke
Mar 28, 2017·SLAS Discovery·Yuji Shimizu, Masaharu Nakayama
Oct 23, 2013·The Journal of Biological Chemistry·Sudarshan RajagopalTom S Wehrman
Dec 25, 2015·Journal of Leukocyte Biology·Caroline A AndersonJames E Pease
Nov 30, 2020·Cellular Signalling·Dylan Scott EigerSudarshan Rajagopal

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