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Activation of G Proteins by Guanine Nucleotide Exchange Factors Relies on GTPase Activity

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 p...

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Detalles Bibliográficos
Autores principales: Stanley, Rob J., Thomas, Geraint M. H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4795700/
https://www.ncbi.nlm.nih.gov/pubmed/26986850
http://dx.doi.org/10.1371/journal.pone.0151861
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author Stanley, Rob J.
Thomas, Geraint M. H.
author_facet Stanley, Rob J.
Thomas, Geraint M. H.
author_sort Stanley, Rob J.
collection PubMed
description 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.
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spelling pubmed-47957002016-03-23 Activation of G Proteins by Guanine Nucleotide Exchange Factors Relies on GTPase Activity Stanley, Rob J. Thomas, Geraint M. H. PLoS One Research Article 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. Public Library of Science 2016-03-17 /pmc/articles/PMC4795700/ /pubmed/26986850 http://dx.doi.org/10.1371/journal.pone.0151861 Text en © 2016 Stanley, Thomas http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Stanley, Rob J.
Thomas, Geraint M. H.
Activation of G Proteins by Guanine Nucleotide Exchange Factors Relies on GTPase Activity
title Activation of G Proteins by Guanine Nucleotide Exchange Factors Relies on GTPase Activity
title_full Activation of G Proteins by Guanine Nucleotide Exchange Factors Relies on GTPase Activity
title_fullStr Activation of G Proteins by Guanine Nucleotide Exchange Factors Relies on GTPase Activity
title_full_unstemmed Activation of G Proteins by Guanine Nucleotide Exchange Factors Relies on GTPase Activity
title_short Activation of G Proteins by Guanine Nucleotide Exchange Factors Relies on GTPase Activity
title_sort activation of g proteins by guanine nucleotide exchange factors relies on gtpase activity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4795700/
https://www.ncbi.nlm.nih.gov/pubmed/26986850
http://dx.doi.org/10.1371/journal.pone.0151861
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