Stanley, R;
Thomas, GM;
(2016)
Activation of G Proteins by Guanine Nucleotide Exchange Factors Relies on GTPase Activity.
PLoS ONE
, 11
(3)
, Article e0151861. 10.1371/journal.pone.0151861.
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Abstract
G proteins are an important family of signalling molecules controlled by guanine nucleotide exchange and GTPase activity in what is commonly called an ‘activation/inactivation cycle’. The molecular mechanism by which guanine nucleotide exchange factors (GEFs) catalyse the activation of monomeric G proteins is well-established, however the complete reversibility of this mechanism is often overlooked. Here, we use a theoretical approach to prove that GEFs are unable to positively control G protein systems at steady-state in the absence of GTPase activity. Instead, positive regulation of G proteins must be seen as a product of the competition between guanine nucleotide exchange and GTPase activity—emphasising a central role for GTPase activity beyond merely signal termination. We conclude that a more accurate description of the regulation of G proteins via these processes is as a ‘balance/imbalance’ mechanism. This result has implications for the understanding of intracellular signalling processes, and for experimental strategies that rely on modulating G protein systems.
Type: | Article |
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Title: | Activation of G Proteins by Guanine Nucleotide Exchange Factors Relies on GTPase Activity. |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1371/journal.pone.0151861 |
Publisher version: | http://dx.doi.org/10.1371/journal.pone.0151861 |
Language: | English |
Additional information: | Copyright © 2016 Stanley, Thomas. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
Keywords: | G protein, GEF, GAP, Model, Guanine nucleotide exchange factor, GTPase activating protein |
UCL classification: | UCL UCL > Provost and Vice Provost Offices UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology |
URI: | https://discovery.ucl.ac.uk/id/eprint/1476829 |
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