BioModelsapplication/xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000173?filename=curation_notes.txthttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000173?filename=BIOMD0000000173.pdfhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000173?filename=BIOMD0000000173-biopax3.owlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000173?filename=BIOMD0000000173-biopax2.owlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000173?filename=manifest.xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000173?filename=BIOMD0000000173_url.xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000173?filename=metadata.rdfhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000173?filename=curation_image.pnghttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000173?filename=BIOMD0000000173.pnghttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000173?filename=BIOMD0000000173-octave.mhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000173?filename=BIOMD0000000173_url.sedmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000173?filename=BIOMD0000000173.odehttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000173?filename=BIOMD0000000173.mhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000173?filename=BIOMD0000000173-matlab.mprimaryOK200Bernhard SchmiererManually curatedordinary differential equation modelL2V1https://www.ebi.ac.uk/biomodels/BIOMD000000017318443295falseBioModelsSBMLModelsSchmierer 2008 Smad Tgfb2008MODEL0451870146Bernhard Schmierer, Alexander L Tournier, Paul A Bates, Caroline S HillBernhard Schmierer18443295, TGF-beta-induced Smad signal transduction from the membrane into the nucleus is not linear and unidirectional, but rather a dynamic network that couples Smad phosphorylation and dephosphorylation through continuous nucleocytoplasmic shuttling of Smads. To understand the quantitative behavior of this network, we have developed a tightly constrained computational model, exploiting the interplay between mathematical modeling and experimental strategies. The model simultaneously reproduces four distinct datasets with excellent accuracy and provides mechanistic insights into how the network operates. We use the model to make predictions about the outcome of fluorescence recovery after photobleaching experiments and the behavior of a functionally impaired Smad2 mutant, which we then verify experimentally. Successful model performance strongly supports the hypothesis of a dynamic maintenance of Smad nuclear accumulation during active signaling. The presented work establishes Smad nucleocytoplasmic shuttling as a dynamic network that flexibly transmits quantitative features of the extracellular TGF-beta signal, such as its duration and intensity, into the nucleus.. 18, 105. Developmental Signalling Laboratory and Biomolecular Modelling Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, United Kingdom.Bernhard.Schmierer@ymail.comDevelopmental Signalling Lab, Cancer Research UK London Research InstituteBIOMD0000000173TGF-beta-induced Smad signal transduction from the membrane into the nucleus is not linear and unidirectional, but rather a dynamic network that couples Smad phosphorylation and dephosphorylation through continuous nucleocytoplasmic shuttling of Smads. To understand the quantitative behavior of this network, we have developed a tightly constrained computational model, exploiting the interplay between mathematical modeling and experimental strategies. The model simultaneously reproduces four distinct datasets with excellent accuracy and provides mechanistic insights into how the network operates. We use the model to make predictions about the outcome of fluorescence recovery after photobleaching experiments and the behavior of a functionally impaired Smad2 mutant, which we then verify experimentally. Successful model performance strongly supports the hypothesis of a dynamic maintenance of Smad nuclear accumulation during active signaling. The presented work establishes Smad nucleocytoplasmic shuttling as a dynamic network that flexibly transmits quantitative features of the extracellular TGF-beta signal, such as its duration and intensity, into the nucleus.Mathematical modeling identifies Smad nucleocytoplasmic shuttling as a dynamic signal-interpreting system.Schmierer Bernhard B, Tournier Alexander L AL, Bates Paul A PA, Hill Caroline S CSfalseSchmierer_2008_Smad_Tgfb This sbml file describes the RECI model from: "Mathematical modeling identifies Smad nucleocytoplasmic shuttling as a dynamic signal-interpreting system" by Bernhard Schmierer, Alexander L. Tournier, Paul A. Bates and Caroline S. Hill, Proc Natl Acad Sci U S A. 2008 May 6;105(18):6608-13. All parameter and species names are as in Figure S3 of the original publication. The original model was done in copasi. SB-431542 addition to a concentration of 10000 nM is set at 2700 sec. The initial concentration of SB, the time point of addition and the final concentration can be set by altering the parameters SB_0, t_SB and SB_end. This model file has been used to reproduce Figures 2D and 5A from the research paper using SBMLodesolver. To get the results for the figures, sum the corresponding concentrations: fig 2D: nuclear EGFP-Smad2 = G_n + pG_n + G2_n + G4_n + 2* GG_n fig 5A (either n or c for nucleus or cytosol): monomeric Smad2 = S2_n/c + G_n/c monomeric P-Smad2 = pS2_n/c + pG_n/c Smad2/Smad4 complexes = S24_n/c + G4_n/c Smad2/Smad2 complexes = S22_n/c + G2_n/c + GG_n/c This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2009 The BioModels Team. For more information see the terms of use. To cite BioModels Database, please use Le Novère N., Bornstein B., Broicher A., Courtot M., Donizelli M., Dharuri H., Li L., Sauro H., Schilstra M., Shapiro B., Snoep J.L., Hucka M. (2006) BioModels Database: A Free, Centralized Database of Curated, Published, Quantitative Kinetic Models of Biochemical and Cellular Systems Nucleic Acids Res., 34: D689-D691. 2024-08-212024-09-022008-06-04BIOMD00000001733.1.3.162.7.11.30hsa0435018443295MODEL0451870146BIOMD0000000173GO:0043234GO:0007179GO:0005634GO:0005737GO:0004721GO:0030291GO:0006913GO:0004675GO:0006461GO:0004722GO:0005160GO:0030512C005629606Q13485Q15796P35813P01137P61812P10600Q8NER5P36897Q5T7S2P37173IPR000786