biostudies-otherUnknown273Lucian SmithThe FEBS journal3915-3926cellular organismshttps://www.ebi.ac.uk/biostudies/studies/MODEL1008100000biostudies-other16934033Lucian SmithVijayalakshmi ChelliahfalseOrtega2006 - bistability from double phosphorylation in signal transduction<notes xmlns="http://www.sbml.org/sbml/level2/version4"> <body xmlns="http://www.w3.org/1999/xhtml"> <div class="dc:title">Ortega2006 - bistability from doublephosphorylation in signal transduction</div> <div class="dc:bibliographicCitation"> <p>This model is described in the article:</p> <div class="bibo:title"> <a href="http://identifiers.org/pubmed/16934033" title="Access to this publication">Bistability from double phosphorylation in signal transduction. Kinetic and structural requirements.</a> </div> <div class="bibo:authorList">Ortega F, Garcés JL, Mas F, Kholodenko BN, Cascante M.</div> <div class="bibo:Journal">FEBS J. 2006 Sep; 273(17): 3915-3926</div> <p>Abstract:</p> <div class="bibo:abstract"> <p>Previous studies have suggested that positive feedback loops and ultrasensitivity are prerequisites for bistability in covalent modification cascades. However, it was recently shown that bistability and hysteresis can also arise solely from multisite phosphorylation. Here we analytically demonstrate that double phosphorylation of a protein (or other covalent modification) generates bistability only if: (a) the two phosphorylation (or the two dephosphorylation) reactions are catalyzed by the same enzyme; (b) the kinetics operate at least partly in the zero-order region; and (c) the ratio of the catalytic constants of the phosphorylation and dephosphorylation steps in the first modification cycle is less than this ratio in the second cycle. We also show that multisite phosphorylation enlarges the region of kinetic parameter values in which bistability appears, but does not generate multistability. In addition, we conclude that a cascade of phosphorylation/dephosphorylation cycles generates multiple steady states in the absence of feedback or feedforward loops. Our results show that bistable behavior in covalent modification cascades relies not only on the structure and regulatory pattern of feedback/feedforward loops, but also on the kinetic characteristics of their component proteins.</p> </div> </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://identifiers.org/biomodels.db/BIOMD0000000258">BIOMD0000000258</a>.</p> <p>To cite BioModels Database, please use: <a href="http://identifiers.org/pubmed/20587024" title="Latest BioModels Database publication">BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models</a>.</p> </div> <div class="dc:license"> <p>To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain 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 Domain Dedication</a> for more information.</p> </div></body></notes>2010-08-10T00:00:00Z2025-07-15T11:06:32.147Z2025-03-29T10:13:55.581ZMODEL1008100000BIOMD000000025816934033C00562C00017CHEBI:16541MAMO_0000046GO:0006468131567