biostudies-otherUnknown21Lucian SmithCellular signalling1151-1160Schizosaccharomyces pombehttps://www.ebi.ac.uk/biostudies/studies/MODEL1212040001biostudies-other19285552Lucian SmithManuel Esparza-FrancofalseSmith2009 - RGS mediated GTP hydrolysis<notes xmlns="http://www.sbml.org/sbml/level2/version4"> <body xmlns="http://www.w3.org/1999/xhtml"> <div class="dc:title">Smith2009 - RGS mediated GTP hydrolysis</div> <div class="dc:bibliographicCitation"> <p>This model is described in the article:</p> <div class="bibo:title"> <a href="http://identifiers.org/pubmed/19285552" title="Access to this publication">Dual positive and negative regulation of GPCR signaling by GTP hydrolysis.</a> </div> <div class="bibo:authorList">Smith B, Hill C, Godfrey EL, Rand D, van den Berg H, Thornton S, Hodgkin M, Davey J, Ladds G.</div> <div class="bibo:Journal">Cell Signal. 2009 Jul;21(7):1151-60.</div> <p>Abstract:</p> <div class="bibo:abstract"> <p>G protein-coupled receptors (GPCRs) regulate a variety of intracellular pathways through their ability to promote the binding of GTP to heterotrimeric G proteins. Regulator of G protein signaling (RGS) proteins increases the intrinsic GTPase activity of Galpha-subunits and are widely regarded as negative regulators of G protein signaling. Using yeast we demonstrate that GTP hydrolysis is not only required for desensitization, but is essential for achieving a high maximal (saturated level) response. Thus RGS-mediated GTP hydrolysis acts as both a negative (low stimulation) and positive (high stimulation) regulator of signaling. To account for this we generated a new kinetic model of the G protein cycle where Galpha(GTP) enters an inactive GTP-bound state following effector activation. Furthermore, in vivo and in silico experimentation demonstrates that maximum signaling output first increases and then decreases with RGS concentration. This unimodal, non-monotone dependence on RGS concentration is novel. Analysis of the kinetic model has revealed a dynamic network motif that shows precisely how inclusion of the inactive GTP-bound state for the Galpha produces this unimodal relationship.</p> </div> </div> <div class="bm:curation"> <p>To reproduce dose-response plots in the publication, the model is simulated with 12 different concentrations (see parameter Ligand_conc). For each concentration, a single value must be obtained from the integral of the trajectory of species z3 from time=0 to time=30. These values are then used to build a dose-response plot (authors used GraphPad Prism). Mutant strains are simulated with alternative parameter values or initial conditions in Table S3.</p> </div> <div class="dc:publisher"> <p>This model is hosted on <a href="http://www.ebi.ac.uk/biomodels">BioModels Database</a> and identified by: <a href="http://www.ebi.ac.uk/biomodels/MODEL1212040001">MODEL1212040001</a> . </p> <p>To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. PMID: <a href="http://identifiers.org/pubmed/20587024">20587024</a> . </p> </div> <div class="dc:license"> <p>To the extent possible under law, all copyright and related orneighbouring rights to this encoded model have been dedicated to the publicdomain worldwide. Please refer to <a href="http://creativecommons.org/publicdomain/zero/1.0/" title="Access to: CC0 1.0 Universal (CC0 1.0), Public Domain Dedication">CC0 Public DomainDedication</a> for more information. </p> </div> </body> </notes>2012-12-04T00:00:00Z2025-07-15T10:04:59.292Z2025-03-29T12:41:56.226ZMODEL1212040001BIOMD0000000439SBO:0000280SBO:0000459SBO:00003471928555212446706CHEBI:15996CHEBI:18367CHEBI:17552MAMO_0000046GO:0005623GO:0005834GO:0043235GO:0008277GO:0004872PATO:00023554896P63211P62873P04695IPR000276IPR000342