Model Identifier
BIOMD0000000032
Short description

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.

Format
SBML (L2V4)
Related Publication
  • Modelling the dynamics of the yeast pheromone pathway.
  • Kofahl B, Klipp E
  • Yeast (Chichester, England) , 7/ 2004 , Volume 21 , pages: 831-850 , PubMed ID: 15300679
  • Humboldt University Berlin, Theoretical Biophysics, Invalidenstrasse 43, 10115 Berlin, Germany.
  • 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.
Contributors
Harish Dharuri

Metadata information

is
BioModels Database MODEL6618819961
BioModels Database BIOMD0000000032
isDescribedBy
PubMed 15300679
hasTaxon
isVersionOf
Gene Ontology response to pheromone
hasPart
Gene Ontology MAPK cascade

Curation status
Curated

Tags
Name Description Size Actions

Model files

BIOMD0000000032_url.xml SBML L2V4 representation of Kofahl2004_PheromonePathway 96.89 KB Preview | Download

Additional files

BIOMD0000000032-biopax3.owl Auto-generated BioPAX (Level 3) 146.10 KB Preview | Download
BIOMD0000000032.xpp Auto-generated XPP file 11.76 KB Preview | Download
BIOMD0000000032.m Auto-generated Octave file 17.09 KB Preview | Download
BIOMD0000000032_urn.xml Auto-generated SBML file with URNs 93.79 KB Preview | Download
BIOMD0000000032.png Auto-generated Reaction graph (PNG) 634.94 KB Preview | Download
BIOMD0000000032-biopax2.owl Auto-generated BioPAX (Level 2) 92.23 KB Preview | Download
BIOMD0000000032.sci Auto-generated Scilab file 194.00 Bytes Preview | Download
BIOMD0000000032.pdf Auto-generated PDF file 370.00 KB Preview | Download
BIOMD0000000032.vcml Auto-generated VCML file 149.15 KB Preview | Download
BIOMD0000000032.svg Auto-generated Reaction graph (SVG) 129.77 KB Preview | Download

  • Model originally submitted by : Harish Dharuri
  • Submitted: 13-Sep-2005 14:40:54
  • Last Modified: 08-Apr-2016 16:19:46
Revisions
  • Version: 2 public model Download this version
    • Submitted on: 08-Apr-2016 16:19:46
    • Submitted by: Harish Dharuri
    • With comment: Current version of Kofahl2004_PheromonePathway
  • Version: 1 public model Download this version
    • Submitted on: 13-Sep-2005 14:40:54
    • Submitted by: Harish Dharuri
    • With comment: Original import of Kofahl2004_pheromone

(*) You might be seeing discontinuous revisions as only public revisions are displayed here. Any private revisions unpublished model revision of this model will only be shown to the submitter and their collaborators.

Legends
: Variable used inside SBML models


Species
Reactions
Reactions Rate Parameters
Ste2a => p compartment*Ste2a*k4 k4=0.24 min_inv
GaGDP + Gbc => Gabc compartment*GaGDP*Gbc*k9 k9=2000.0 min_inv_nM_inv
Gabc => GaGTP + Gbc; Ste2a compartment*Ste2a*Gabc*k6 k6=0.0036 min_inv_nM_inv
Gbc + complexC => complexD compartment*Gbc*complexC*k10 k10=0.1 min_inv_nM_inv
complexD => Gbc + complexC compartment*complexD*k11 k11=5.0 min_inv
complexE => Gbc + Ste7 + Ste5 + Fus3 + Ste20 + Ste11 compartment*complexE*k21 k21=5.0 min_inv
complexG => Gbc + Ste7 + Ste5 + Fus3 + Ste20 + Ste11 compartment*complexG*k25 k25=5.0 min_inv
complexL => Gbc + Ste7 + Ste5 + Ste20 + Ste11 compartment*complexL*k32 k32=5.0 min_inv
GaGTP => GaGDP compartment*GaGTP*k7 k7=0.24 min_inv
Ste11 + Ste5 => complexA compartment*Ste5*Ste11*k12 k12=1.0 min_inv_nM_inv
complexA => Ste11 + Ste5 compartment*complexA*k13 k13=3.0 min_inv
complexH => Gbc + Ste7 + Ste5 + Fus3 + Ste20 + Ste11 compartment*complexH*k27 k27=5.0 min_inv
Curator's comment:
(added: 21 Oct 2010, 15:49:41, updated: 21 Oct 2010, 15:49:41)
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).