title: Activation of G Proteins by Guanine Nucleotide Exchange Factors Relies on GTPase Activity.
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.
authors.affiliation: CoMPLEX, University College London, London, United Kingdom.|Department of Cell & Developmental Biology, University College London, London, United Kingdom.
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Stanley
authors.affiliation: CoMPLEX, University College London, London, United Kingdom.|Department of Cell & Developmental Biology, University College London, London, United Kingdom.
authors.forename: Geraint M H
authors.initials: GM
authors.lastname: Thomas
mesh_terms: D000818:Animals; D020558:GTP Phosphohydrolases / Q000378:metabolism / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D020662:Guanine Nucleotide Exchange Factors / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D015533:Transcriptional Activation / Q000502:physiology
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins