Modelling the consequences of receptor-G-protein promiscuity

Trends in Pharmacological Sciences
Stanislav TucekViktorie Vlachová

Abstract

Many G-protein-coupled receptors interact with more than one type of G protein, giving rise to extreme variability in the effects of receptor activation, depending on, for example, receptor density and desensitization, efficacy of agonists, and availability of specific G proteins. This leads to errors in interpretation of data. To facilitate understanding the consequences of receptor-G-protein promiscuity, we use two simplified models to simulate such consequences. Applied to the regulation of adenylyl cyclase and phosphoinositidase, the models predict seemingly paradoxical situations and explain some phenomena that, at first sight, might seem to require the induction of agonist-specific (G-protein-selective) receptor conformations.

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Citations

Jun 28, 2006·Bulletin of Mathematical Biology·C Y Chen, J R King
Jan 31, 2004·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Michel A PontariMichael R Ruggieri
Nov 17, 2012·American Journal of Respiratory and Critical Care Medicine·Nadine WickboldtDeborah Pugin
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Dec 8, 2017·Bulletin of Mathematical Biology·Gilles Gnacadja
Feb 16, 2017·Frontiers in Molecular Neuroscience·Philip F Copenhaver, Donat Kögel
Apr 11, 2018·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Luigino CalzettaMaria Gabriella Matera

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