ArticleProceedings of the National Academy of Sciences of the United States of America2004
Computational modeling reveals how interplay between components of a GTPase-cycle module regulates signal transduction.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 43 citations in OpenAlex.
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- Regulating cellular cyclic adenosine monophosphate: "Sources," "sinks," and now, "tunable valves".Wiley interdisciplinary reviews. Systems biology and medicine · 2020Review
- Modelling and simulation of biased agonism dynamics at a G protein-coupled receptor.Journal of theoretical biology · 2018Article
- G proteins in reverse mode: receptor-mediated GTP release inhibits G protein and effector function.The Journal of biological chemistry · 2010Article
- Kinetics of M1 muscarinic receptor and G protein signaling to phospholipase C in living cells.The Journal of general physiology · 2010Article
- Design of versatile biochemical switches that respond to amplitude, duration, and spatial cues.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Mixed-integer nonlinear optimisation approach to coarse-graining biochemical networks.IET systems biology · 2009Article
- Collision coupling, crosstalk, and compartmentalization in G-protein coupled receptor systems: can a single model explain disparate results?Journal of theoretical biology · 2008Article
- Article
- Coordinate regulation of G protein signaling via dynamic interactions of receptor and GAP.PLoS computational biology · 2008Article
- Diffusion-limited reactions in G-protein activation: unexpected consequences of antagonist and agonist competition.Journal of theoretical biology · 2008Article
- The signaling petri net-based simulator: a non-parametric strategy for characterizing the dynamics of cell-specific signaling networks.PLoS computational biology · 2008Article
- A kinetic model for calcium dynamics in RAW 264.7 cells: 1. Mechanisms, parameters, and subpopulational variability.Biophysical journal · 2007Article
- A kinetic model for calcium dynamics in RAW 264.7 cells: 2. Knockdown response and long-term response.Biophysical journal · 2007Article
- Review
- Both ligand- and cell-specific parameters control ligand agonism in a kinetic model of g protein-coupled receptor signaling.PLoS computational biology · 2007Article
- Computational model explains high activity and rapid cycling of Rho GTPases within protein complexes.PLoS computational biology · 2006Article
- Cell-signalling dynamics in time and space.Nature reviews. Molecular cell biology · 2006Review
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
Abstract
Heterotrimeric G protein signaling is regulated by signaling modules composed of heterotrimeric G proteins, active G protein-coupled receptors (Rs), which activate G proteins, and GTPase-activating proteins (GAPs), which deactivate G proteins. We term these modules GTPase-cycle modules. The local concentrations of these proteins are spatially regulated between plasma membrane microdomains and between the plasma membrane and cytosol, but no data or models are available that quantitatively explain the effect of such regulation on signaling. We present a computational model of the GTPase-cycle module that predicts that the interplay of local G protein, R, and GAP concentrations gives rise to 16 distinct signaling regimes and numerous intermediate signaling phenomena. The regimes suggest alternative modes of the GTPase-cycle module that occur based on defined local concentrations of the component proteins. In one mode, signaling occurs while G protein and receptor are unclustered and GAP eliminates signaling; in another, G protein and receptor are clustered and GAP can rapidly modulate signaling but does not eliminate it. Experimental data from multiple GTPase-cycle modules is interpreted in light of these predictions. The latter mode explains previously paradoxical data in which GAP does not alter maximal current amplitude of G protein-activated ion channels, but hastens signaling. The predictions indicate how variations in local concentrations of the component proteins create GTPase-cycle modules with distinctive phenotypes. They provide a quantitative framework for investigating how regulation of local concentrations of components of the GTPase-cycle module affects signaling.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.