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BIOMD0000000032 - Kofahl2004_PheromonePathway

 

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Reference Publication
Publication ID: 15300679
Kofahl B, Klipp E.
Modelling the dynamics of the yeast pheromone pathway.
Yeast 2004 Jul; 21(10): 831-850
Humboldt University Berlin, Theoretical Biophysics, Invalidenstrasse 43, 10115 Berlin, Germany.  [more]
Model
Original Model: BIOMD0000000032.xml.origin
Submitter: Harish Dharuri
Submission ID: MODEL6618819961
Submission Date: 13 Sep 2005 13:40:54 UTC
Last Modification Date: 15 May 2012 21:43:57 UTC
Creation Date: 08 Jun 2005 14:45:16 UTC
Encoders:  Harish Dharuri
   Jacky L Snoep
set #1
bqbiol:hasPart Gene Ontology MAPK cascade
set #2
bqbiol:hasTaxon Taxonomy Saccharomyces cerevisiae
set #3
bqbiol:isVersionOf Gene Ontology response to pheromone
Notes

This a model from the article:
Modelling the dynamics of the yeast pheromone pathway.
Kofahl B, Klipp E Yeast[2004 Jul; Volume: 21 (Issue: 10 )] Page info: 831-50 15300679,
Abstract:
We present a mathematical model of the dynamics of the pheromone pathways in haploid yeast cells of mating type MATa after stimulation with pheromone alpha-factor. The model consists of a set of differential equations and describes the dynamics of signal transduction from the receptor via several steps, including a G protein and a scaffold MAP kinase cascade, up to changes in the gene expression after pheromone stimulation in terms of biochemical changes (complex formations, phosphorylations, etc.). The parameters entering the models have been taken from the literature or adapted to observed time courses or behaviour. Using this model we can follow the time course of the various complex formation processes and of the phosphorylation states of the proteins involved. Furthermore, we can explain the phenotype of more than a dozen well-characterized mutants and also the graded response of yeast cells to varying concentrations of the stimulating pheromone.


The model was updated on 21st October 2010, by Vijayalakshmi Chelliah.
The following changes were made: 1) The model has been converted to SBML l2v4. 2) The model has been recurated and the curation figure was updated (units are in nanoMolar; but the publication has units in microMolar). Simulations were done using Copasi v4.6 (Build 32). 3) Notes have been added. 4) Annotation for one of the species has been corrected (Complex M).



SBML level 2 code generated for the JWS Online project by Jacky Snoep using PySCeS
Run this model online at http://jjj.biochem.sun.ac.za
To cite JWS Online please refer to: Olivier, B.G. and Snoep, J.L. (2004) Web-based modelling using JWS Online, Bioinformatics, 20:2143-2144

The following are the four major differences between the original publication by Kofahl et al and the model that actually is able to replicate the results as depicted in the publication (those corrections have been made in agreement with the authors):
1. Bar1 is the inactive protease present inside the cell but the publication wrongly mentions that Bar1 is also the protease that is present on the extracellular surface.
The model correctly names the protease in it's different forms by calling inactive Bar1 within the cell as Bar1, active Bar1 within the cell as Bar1a and extracellular Bar1 as Bar1aex
2. The initial amount of Alpha-factor is given as 1000nM but the model uses a value of 100nM.
3. The value of the paramenter k8 is given as 0.33 but the model uses a value of 0.033.
4. The value of the paramenter k41 is given as 0.002 but the model uses a value of 0.02.

This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/).(http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2010 The BioModels.net Team.
For more information see the terms of use.
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

Model
Publication ID: 15300679 Submission Date: 13 Sep 2005 13:40:54 UTC Last Modification Date: 15 May 2012 21:43:57 UTC Creation Date: 08 Jun 2005 14:45:16 UTC
Mathematical expressions
Reactions
alpha degradation v2 v3 v4
v5 v6 v7 v8
v9 v10 v11 v12
v13 v14 v15 v16
v17 v18 v19 v20
v21 v22 v23 v24
v25 v26 v27 v28
v29 v30 v31 v32
v33 v34 v35 v36
v37 v38 v39 v40
v41 v42 v43 v44
v45 v46 v47  
Physical entities
Compartments Species
Extracellular α-factor Bar1activeEx  
cell Ste2 Ste2active Gαβγ
GαGTP Gβγ GαGDP
complexC complexD Ste5
Ste11 complexA Ste7
Fus3 complexB Ste20
complexE complexF complexG
complexH complexI complexL
Fus3PP complexK Ste12
Ste12active Bar1 Bar1active
Far1 Far1PP Far1ubiquitin
complexM complexN Cdc28
Sst2 p  
Reactions (47)
 
 alpha degradation [α-factor] ↔ ;   {Bar1activeEx}
 
 v2 [Ste2] ↔ [Ste2active];   {α-factor}
 
 v3 [Ste2active] ↔ [Ste2];  
 
 v4 [Ste2active] ↔ [p];  
 
 v5 [Ste2] ↔ ;  
 
 v6 [Gαβγ] ↔ [GαGTP] + [Gβγ];   {Ste2active}
 
 v7 [GαGTP] ↔ [GαGDP];  
 
 v8 [GαGTP] ↔ [GαGDP];   {Sst2}
 
 v9 [GαGDP] + [Gβγ] ↔ [Gαβγ];  
 
 v10 [Gβγ] + [complexC] ↔ [complexD];  
 
 v11 [complexD] ↔ [Gβγ] + [complexC];  
 
 v12 [Ste11] + [Ste5] ↔ [complexA];  
 
 v13 [complexA] ↔ [Ste11] + [Ste5];  
 
 v14 [Fus3] + [Ste7] ↔ [complexB];  
 
 v15 [complexB] ↔ [Fus3] + [Ste7];  
 
 v16 [complexA] + [complexB] ↔ [complexC];  
 
 v17 [complexC] ↔ [Fus3] + [Ste11] + [Ste7] + [Ste5];  
 
 v18 [complexD] + [Ste20] ↔ [complexE];  
 
 v19 [complexE] ↔ [complexD] + [Ste20];  
 
 v20 [complexE] ↔ [complexF];  
 
 v21 [complexE] ↔ [Gβγ] + [Ste7] + [Ste5] + [Fus3] + [Ste20] + [Ste11];  
 
 v22 [complexF] ↔ [complexG];  
 
 v23 [complexF] ↔ [Gβγ] + [Ste7] + [Ste5] + [Fus3] + [Ste20] + [Ste11];  
 
 v24 [complexG] ↔ [complexH];  
 
 v25 [complexG] ↔ [Gβγ] + [Ste7] + [Ste5] + [Fus3] + [Ste20] + [Ste11];  
 
 v26 [complexH] ↔ [complexI];  
 
 v27 [complexH] ↔ [Gβγ] + [Ste7] + [Ste5] + [Fus3] + [Ste20] + [Ste11];  
 
 v28 [complexI] ↔ [complexL] + [Fus3PP];  
 
 v29 [complexL] + [Fus3] ↔ [complexK];  
 
 v30 [complexK] ↔ [complexL] + [Fus3];  
 
 v31 [complexK] ↔ [complexI];  
 
 v32 [complexL] ↔ [Gβγ] + [Ste7] + [Ste5] + [Ste20] + [Ste11];  
 
 v33 [Fus3PP] ↔ [Fus3];  
 
 v34 [Ste12] + [Fus3PP] ↔ [Ste12active];  
 
 v35 [Ste12active] ↔ [Ste12] + [Fus3PP];  
 
 v36 [Bar1] ↔ [Bar1active];   {Ste12active}
 
 v37 [Bar1active] ↔ [Bar1];  
 
 v38 [Bar1active] ↔ [Bar1activeEx];  
 
 v39 [Far1] ↔ [Far1PP];   {Fus3PP}
 
 v40 [Far1PP] ↔ [Far1];  
 
 v41 [Far1] ↔ [Far1ubiquitin];   {Cdc28}
 
 v42 [Gβγ] + [Far1PP] ↔ [complexM];  
 
 v43 [complexM] ↔ [Gβγ] + [Far1PP];  
 
 v44 [complexN] ↔ [Cdc28] + [Far1PP];  
 
 v45 [Cdc28] + [Far1PP] ↔ [complexN];  
 
 v46 [p] ↔ [Sst2];   {Fus3PP}
 
 v47 [Sst2] ↔ [p];  
 
  Spatial dimensions: 3.0  Compartment size: 1.0
 
   α-factor
Compartment: Extracellular
Initial concentration: 100.0
 
 Bar1activeEx
Compartment: Extracellular
Initial concentration: 0.0
 
 cell Spatial dimensions: 3.0  Compartment size: 1.0
 
 Ste2
Compartment: cell
Initial concentration: 1666.6666667
 
 Ste2active
Compartment: cell
Initial concentration: 0.0
 
 Gαβγ
Compartment: cell
Initial concentration: 1666.6666667
 
 GαGTP
Compartment: cell
Initial concentration: 0.0
 
 Gβγ
Compartment: cell
Initial concentration: 0.0
 
 GαGDP
Compartment: cell
Initial concentration: 0.0
 
 complexC
Compartment: cell
Initial concentration: 235.724935791903
 
 complexD
Compartment: cell
Initial concentration: 0.0
 
 Ste5
Compartment: cell
Initial concentration: 158.33176608789
 
 Ste11
Compartment: cell
Initial concentration: 158.33176608789
 
 complexA
Compartment: cell
Initial concentration: 105.943298120207
 
 Ste7
Compartment: cell
Initial concentration: 36.3997016405141
 
 Fus3
Compartment: cell
Initial concentration: 686.399701640513
 
 complexB
Compartment: cell
Initial concentration: 77.8753625675829
 
 Ste20
Compartment: cell
Initial concentration: 1000.0
 
 complexE
Compartment: cell
Initial concentration: 0.0
 
 complexF
Compartment: cell
Initial concentration: 0.0
 
 complexG
Compartment: cell
Initial concentration: 0.0
 
 complexH
Compartment: cell
Initial concentration: 0.0
 
 complexI
Compartment: cell
Initial concentration: 0.0
 
 complexL
Compartment: cell
Initial concentration: 0.0
 
 Fus3PP
Compartment: cell
Initial concentration: 0.0
 
 complexK
Compartment: cell
Initial concentration: 0.0
 
 Ste12
Compartment: cell
Initial concentration: 200.0
 
 Ste12active
Compartment: cell
Initial concentration: 0.0
 
 Bar1
Compartment: cell
Initial concentration: 200.0
 
 Bar1active
Compartment: cell
Initial concentration: 0.0
 
 Far1
Compartment: cell
Initial concentration: 500.0
 
 Far1PP
Compartment: cell
Initial concentration: 0.0
 
 Far1ubiquitin
Compartment: cell
Initial concentration: 0.0
 
 complexM
Compartment: cell
Initial concentration: 0.0
 
 complexN
Compartment: cell
Initial concentration: 0.0
 
 Cdc28
Compartment: cell
Initial concentration: 300.0
 
 Sst2
Compartment: cell
Initial concentration: 0.0
 
   p
Compartment: cell
Initial concentration: 0.0
 
alpha degradation (1)
 
   k1
Value: 0.03   (Units: min_inv_nM_inv)
Constant
 
v2 (1)
 
   k2
Value: 0.0012   (Units: min_inv_nM_inv)
Constant
 
v3 (1)
 
   k3
Value: 0.6   (Units: min_inv)
Constant
 
v4 (1)
 
   k4
Value: 0.24   (Units: min_inv)
Constant
 
v5 (1)
 
   k5
Value: 0.024   (Units: min_inv)
Constant
 
v6 (1)
 
   k6
Value: 0.0036   (Units: min_inv_nM_inv)
Constant
 
v7 (1)
 
   k7
Value: 0.24   (Units: min_inv)
Constant
 
v8 (1)
 
   k8
Value: 0.033   (Units: min_inv_nM_inv)
Constant
 
v9 (1)
 
   k9
Value: 2000.0   (Units: min_inv_nM_inv)
Constant
 
v10 (1)
 
   k10
Value: 0.1   (Units: min_inv_nM_inv)
Constant
 
v11 (1)
 
   k11
Value: 5.0   (Units: min_inv)
Constant
 
v12 (1)
 
   k12
Value: 1.0   (Units: min_inv_nM_inv)
Constant
 
v13 (1)
 
   k13
Value: 3.0   (Units: min_inv)
Constant
 
v14 (1)
 
   k14
Value: 1.0   (Units: min_inv_nM_inv)
Constant
 
v15 (1)
 
   k15
Value: 3.0   (Units: min_inv)
Constant
 
v16 (1)
 
   k16
Value: 3.0   (Units: min_inv_nM_inv)
Constant
 
v17 (1)
 
   k17
Value: 100.0   (Units: min_inv)
Constant
 
v18 (1)
 
   k18
Value: 5.0   (Units: min_inv_nM_inv)
Constant
 
v19 (1)
 
   k19
Value: 1.0   (Units: min_inv)
Constant
 
v20 (1)
 
   k20
Value: 10.0   (Units: min_inv)
Constant
 
v21 (1)
 
   k21
Value: 5.0   (Units: min_inv)
Constant
 
v22 (1)
 
   k22
Value: 47.0   (Units: min_inv)
Constant
 
v23 (1)
 
   k23
Value: 5.0   (Units: min_inv)
Constant
 
v24 (1)
 
   k24
Value: 345.0   (Units: min_inv)
Constant
 
v25 (1)
 
   k25
Value: 5.0   (Units: min_inv)
Constant
 
v26 (1)
 
   k26
Value: 50.0   (Units: min_inv)
Constant
 
v27 (1)
 
   k27
Value: 5.0   (Units: min_inv)
Constant
 
v28 (1)
 
   k28
Value: 140.0   (Units: min_inv)
Constant
 
v29 (1)
 
   k29
Value: 10.0   (Units: min_inv_nM_inv)
Constant
 
v30 (1)
 
   k30
Value: 1.0   (Units: min_inv)
Constant
 
v31 (1)
 
   k31
Value: 250.0   (Units: min_inv)
Constant
 
v32 (1)
 
   k32
Value: 5.0   (Units: min_inv)
Constant
 
v33 (1)
 
   k33
Value: 50.0   (Units: min_inv)
Constant
 
v34 (1)
 
   k34
Value: 18.0   (Units: min_inv_nM_inv)
Constant
 
v35 (1)
 
   k35
Value: 10.0   (Units: min_inv)
Constant
 
v36 (1)
 
   k36
Value: 0.1   (Units: min_inv_nM_inv)
Constant
 
v37 (1)
 
   k37
Value: 0.1   (Units: min_inv)
Constant
 
v38 (1)
 
   k38
Value: 0.01   (Units: min_inv)
Constant
 
v39 (1)
 
   k39
Value: 18.0   (Units: min_inv)
Constant
 
v40 (1)
 
   k40
Value: 1.0   (Units: min_inv)
Constant
 
v41 (1)
 
   k41
Value: 0.02   (Units: min_inv_nM_inv)
Constant
 
v42 (1)
 
   k42
Value: 0.1   (Units: min_inv_nM_inv)
Constant
 
v43 (1)
 
   k43
Value: 0.01   (Units: min_inv)
Constant
 
v44 (1)
 
   k44
Value: 0.01   (Units: min_inv)
Constant
 
v45 (1)
 
   k45
Value: 0.1   (Units: min_inv_nM_inv)
Constant
 
v46 (1)
 
   k46
Value: 200.0   (Units: nM_min_inv)
Constant
 
v47 (1)
 
   k47
Value: 1.0   (Units: min_inv)
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000032

Curator's comment: (updated: 21 Oct 2010 15:49:41 BST)

The figures 3 and 6 of the reference publication has been reproduced here. Note that the units are in nanoMolar, whereas the plots in the publications are in microMolar. The model has all the parameters that relates to the wildtype. So, the plots that are reproduced here, denote the wildtype. To get the plots for the mutant variants, change the necessary parameters mentioned in Table 5 of the reference publication and simulate the model. The model was integrated and simulated using Copasi v4.6 (Build 32).

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