Activation of G Proteins by Guanine Nucleotide Exchange Factors Relies on GTPase Activity
Autor: | Rob J, Stanley, Geraint M H, Thomas |
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Rok vydání: | 2015 |
Předmět: |
Transcriptional Activation
Guanine Nucleotide Receptor Signaling Research and Analysis Methods Models Biological Biochemistry GTP Phosphohydrolases Signaling Molecules Cell Signaling GTP-Binding Proteins Biochemical Simulations Animals Guanine Nucleotide Exchange Factors Humans Membrane Receptor Signaling GTPase signaling Nucleotides Simulation and Modeling Biology and Life Sciences Computational Biology Proteins Protein Complexes Cell Biology Kinetics G-Protein Signaling Research Article Signal Transduction |
Zdroj: | PLoS ONE |
ISSN: | 1932-6203 |
Popis: | 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. |
Databáze: | OpenAIRE |
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