BioModelsapplication/xmlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL9079179924?filename=MODEL9079179924.pdfhttps://www.ebi.ac.uk/biomodels/model/download/MODEL9079179924?filename=MODEL9079179924-biopax3.owlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL9079179924?filename=MODEL9079179924-biopax2.owlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL9079179924?filename=MODEL9079179924_url.xmlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL9079179924?filename=MODEL9079179924_urn.xmlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL9079179924?filename=MODEL9079179924.vcmlhttps://www.ebi.ac.uk/biomodels/model/download/MODEL9079179924?filename=MODEL9079179924.mhttps://www.ebi.ac.uk/biomodels/model/download/MODEL9079179924?filename=MODEL9079179924.xpphttps://www.ebi.ac.uk/biomodels/model/download/MODEL9079179924?filename=MODEL9079179924.scihttps://www.ebi.ac.uk/biomodels/model/download/MODEL9079179924?filename=MODEL9079179924.pngprimaryOK200Sharat VayttadenNon-curatedordinary differential equation modelL2V1https://www.ebi.ac.uk/biomodels/MODEL907917992412169734falseBioModelsSBMLModelsBhalla2002 MAPK bistability fig1c2002MODEL9079179924Upinder S Bhalla, Prahlad T Ram, Ravi IyengarUpinder S Bhalla12169734, Intracellular signaling networks receive and process information to control cellular machines. The mitogen-activated protein kinase (MAPK) 1,2/protein kinase C (PKC) system is one such network that regulates many cellular machines, including the cell cycle machinery and autocrine/paracrine factor synthesizing machinery. We used a combination of computational analysis and experiments in mouse NIH-3T3 fibroblasts to understand the design principles of this controller network. We find that the growth factor-stimulated signaling network containing MAPK 1, 2/PKC can operate with one (monostable) or two (bistable) stable states. At low concentrations of MAPK phosphatase, the system exhibits bistable behavior, such that brief stimulus results in sustained MAPK activation. The MAPK-induced increase in the amounts of MAPK phosphatase eliminates the prolonged response capability and moves the network to a monostable state, in which it behaves as a proportional response system responding acutely to stimulus. Thus, the MAPK 1, 2/PKC controller network is flexibly designed, and MAPK phosphatase may be critical for this flexible response.. 5583, 297. National Center for Biological Sciences, Bangalore 560065 India. bhalla@ncbs.res.indoqcs@ncbs.res.inDOQCSIntracellular signaling networks receive and process information to control cellular machines. The mitogen-activated protein kinase (MAPK) 1,2/protein kinase C (PKC) system is one such network that regulates many cellular machines, including the cell cycle machinery and autocrine/paracrine factor synthesizing machinery. We used a combination of computational analysis and experiments in mouse NIH-3T3 fibroblasts to understand the design principles of this controller network. We find that the growth factor-stimulated signaling network containing MAPK 1, 2/PKC can operate with one (monostable) or two (bistable) stable states. At low concentrations of MAPK phosphatase, the system exhibits bistable behavior, such that brief stimulus results in sustained MAPK activation. The MAPK-induced increase in the amounts of MAPK phosphatase eliminates the prolonged response capability and moves the network to a monostable state, in which it behaves as a proportional response system responding acutely to stimulus. Thus, the MAPK 1, 2/PKC controller network is flexibly designed, and MAPK phosphatase may be critical for this flexible response.MAP kinase phosphatase as a locus of flexibility in a mitogen-activated protein kinase signaling network.Bhalla Upinder S US, Ram Prahlad T PT, Iyengar Ravi RfalseBhalla2002_MAPK-bistability-fig1c Model for figure 1c in Bhalla US et al. Science (2002) 297(5583):1018-23.The demo for this figure is available here. This synaptic signaling model is without the MKP-1 feedback, so it is bistable and remains so over long periods. This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. 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. 2011-07-042005-01-012008-03-13MODEL907917992412169734MODEL9079179924GO:000016510090