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BIOMD0000000258 - Ortega2006 - bistability from double phosphorylation in signal transduction

 

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Reference Publication
Publication ID: 16934033
Ortega F, Garcés JL, Mas F, Kholodenko BN, Cascante M.
Bistability from double phosphorylation in signal transduction. Kinetic and structural requirements.
FEBS J. 2006 Sep; 273(17): 3915-3926
Centre for Research in Theoretical Chemistry, Scientific Park of Barcelona, Spain.  [more]
Model
Original Model: BIOMD0000000258.origin
Submitter: Vijayalakshmi Chelliah
Submission ID: MODEL1008100000
Submission Date: 10 Aug 2010 12:59:29 UTC
Last Modification Date: 22 May 2015 13:15:14 UTC
Creation Date: 29 Jul 2010 10:50:32 UTC
Encoders:  Vijayalakshmi Chelliah
   Marta Cascante
set #1
bqbiol:hasTaxon Taxonomy cellular organisms
set #2
bqbiol:isVersionOf Gene Ontology protein phosphorylation
Notes
Ortega2006 - bistability from double phosphorylation in signal transduction

This model is described in the article:

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.

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.

Model
Publication ID: 16934033 Submission Date: 10 Aug 2010 12:59:29 UTC Last Modification Date: 22 May 2015 13:15:14 UTC Creation Date: 29 Jul 2010 10:50:32 UTC
Mathematical expressions
Reactions
v1 v2 v3 v4
Physical entities
Compartments Species
cell alpha beta gamma
Global parameters
r31 r24 Chi14 Ks1
Ks2 Ks3 Ks4 Vm1
p      
Reactions (4)
 
 v1 [alpha] ↔ [beta];  
 
 v2 [beta] ↔ [alpha];   {gamma}
 
 v3 [beta] ↔ [gamma];   {alpha}
 
 v4 [gamma] → [beta];  
 
   cell Spatial dimensions: 3.0  Compartment size: 1.0
 
 alpha
Compartment: cell
Initial concentration: 0.462
 
 beta
Compartment: cell
Initial concentration: 0.2
 
 gamma
Compartment: cell
Initial concentration: 0.338
 
Global Parameters (9)
 
   r31
Value: 1.0
Constant
 
   r24
Value: 1.0
Constant
 
   Chi14
Value: 1.1
Constant
 
   Ks1
Value: 0.01
Constant
 
   Ks2
Value: 0.01
Constant
 
   Ks3
Value: 0.01
Constant
 
   Ks4
Value: 0.01
Constant
 
   Vm1
Value: 1.0
Constant
 
   p
Value: 1.0
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000258

Curator's comment: (updated: 10 Aug 2010 14:03:52 BST)

The figures 5A, 5B and 5C of the reference publication is reproduced. The model was integrated and simulated using Copasi v4.5.31.

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