BioModelsapplication/xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000116?filename=curation_notes.txthttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000116?filename=BIOMD0000000116.pdfhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000116?filename=BIOMD0000000116-biopax3.owlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000116?filename=BIOMD0000000116-biopax2.owlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000116?filename=manifest.xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000116?filename=BIOMD0000000116_url.xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000116?filename=BIOMD0000000116.odehttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000116?filename=BIOMD0000000116.mhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000116?filename=BIOMD0000000116_url.sedmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000116?filename=BIOMD0000000116.vcmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000116?filename=BIOMD0000000116.pnghttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000116?filename=metadata.rdfhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000116?filename=BIOMD0000000116-matlab.mhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000116?filename=curation_image.pnghttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000116?filename=BIOMD0000000116-octave.mhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000116?filename=BIOMD0000000116.sciprimaryOK200Christian WaltermannManually curatedordinary differential equation modelL2V1https://www.ebi.ac.uk/biomodels/BIOMD000000011617259986falseBioModelsSBMLModelsMcClean2007 CrossTalk2007MODEL7321452458Megan N McClean, Areez Mody, James R Broach, Sharad RamanathanMegan N McClean17259986, Cells must respond specifically to different environmental stimuli in order to survive. The signal transduction pathways involved in sensing these stimuli often share the same or homologous proteins. Despite potential cross-wiring, cells show specificity of response. We show, through modeling, that the physiological response of such pathways exposed to simultaneous and temporally ordered inputs can demonstrate system-level mechanisms by which pathways achieve specificity. We apply these results to the hyperosmolar and pheromone mitogen-activated protein (MAP) kinase pathways in the yeast Saccharomyces cerevisiae. These two pathways specifically sense osmolar and pheromone signals, despite sharing a MAPKKK, Ste11, and having homologous MAPKs (Fus3 and Hog1). We show that in a single cell, the pathways are bistable over a range of inputs, and the cell responds to only one stimulus even when exposed to both. Our results imply that these pathways achieve specificity by filtering out spurious cross-talk through mutual inhibition. The variability between cells allows for heterogeneity of the decisions.. 3, 39. FAS Center for Systems Biology, Harvard University, Cambridge, Massachusetts 02138, USA.christian.waltermann@molgen.mpg.deMax Planck Institute For Molecular GeneticsBIOMD0000000116Cells must respond specifically to different environmental stimuli in order to survive. The signal transduction pathways involved in sensing these stimuli often share the same or homologous proteins. Despite potential cross-wiring, cells show specificity of response. We show, through modeling, that the physiological response of such pathways exposed to simultaneous and temporally ordered inputs can demonstrate system-level mechanisms by which pathways achieve specificity. We apply these results to the hyperosmolar and pheromone mitogen-activated protein (MAP) kinase pathways in the yeast Saccharomyces cerevisiae. These two pathways specifically sense osmolar and pheromone signals, despite sharing a MAPKKK, Ste11, and having homologous MAPKs (Fus3 and Hog1). We show that in a single cell, the pathways are bistable over a range of inputs, and the cell responds to only one stimulus even when exposed to both. Our results imply that these pathways achieve specificity by filtering out spurious cross-talk through mutual inhibition. The variability between cells allows for heterogeneity of the decisions.Cross-talk and decision making in MAP kinase pathways.McClean Megan N MN, Mody Areez A, Broach James R JR, Ramanathan Sharad SfalseMcClean2007_CrossTalk This model encoded according to the paper Cross-talk and decision making in MAP kinase pathways. Supplementary Figure 2 has been reproduced by COPASI4.0.20 (development) using parameter scan method. You probably need to uncheck "always use initial conditions" in copasi when you simulate for the second run in order to get the figure. S1 scale from 0 to 12. Keep in mind that the y axis is the fractions of excited X3 and Y3, meaning that X3P and Y3P are normalized by total concentration X3T and Y3T. The results from modeling the pathway in Supplementary Figure1a, including both activation and inhibition. According to the paper, the value of ka and kd should in the orange region (ka belongs [0,1], kd belongs [1,10]) so assigned ka=0, kd=1. The author made the simplifying assumption that the interactions between the pathways are symmetric. Thus the k12xy=k12yx=ka, k33xy=k33yx=kd. 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. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not. 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. 2024-08-212024-09-022007-06-05BIOMD00000001162.7.11.12.7.12.217259986MODEL7321452458BIOMD0000000116GO:0000161GO:0019236GO:0005623GO:0004709GO:0000186GO:0000185GO:0005186GO:0000187GO:0004708GO:0043575GO:0000167GO:0005078GO:00001884932P23561P06784P16892P08018P32485