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Ortega2006 - bistability from double phosphorylation in signal transduction


ABSTRACT: Ortega2006 - bistability from double phosphorylation in signal transduction This model is described in the article: Bistability from double phosphorylation in signal transduction. Kinetic and structural requirements. Ortega F, Garcés JL, Mas F, Kholodenko BN, Cascante M. FEBS J. 2006 Sep; 273(17): 3915-3926 Abstract: 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. This model is hosted on BioModels Database and identified by: BIOMD0000000258. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. 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 CC0 Public Domain Dedication for more information.

SUBMITTER: Vijayalakshmi Chelliah  

PROVIDER: BIOMD0000000258 | BioModels | 2010-07-29

REPOSITORIES: BioModels

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Bistability from double phosphorylation in signal transduction. Kinetic and structural requirements.

Ortega Fernando F   Garcés José L JL   Mas Francesc F   Kholodenko Boris N BN   Cascante Marta M  

The FEBS journal 20060901 17


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  ...[more]

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