BioModelsapplication/xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000146?filename=curation_notes.txthttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000146?filename=BIOMD0000000146.pdfhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000146?filename=BIOMD0000000146-biopax3.owlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000146?filename=BIOMD0000000146-biopax2.owlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000146?filename=BIOMD0000000146_url.xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000146?filename=manifest.xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000146?filename=BIOMD0000000146-octave.mhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000146?filename=BIOMD0000000146.vcmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000146?filename=BIOMD0000000146.odehttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000146?filename=BIOMD0000000146-matlab.mhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000146?filename=BIOMD0000000146_url.sedmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000146?filename=BIOMD0000000146.pnghttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000146?filename=metadata.rdfhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000146?filename=BIOMD0000000146.mhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000146?filename=BIOMD0000000146.scihttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000146?filename=curation_image.pngprimaryOK200Enuo HeManually curatedordinary differential equation modelL2V1https://www.ebi.ac.uk/biomodels/BIOMD000000014612691603falseBioModelsBIOMD0000000019 biomodels.db BIOMD0000000048 biomodels.db BIOMD0000000010 biomodels.dbModelsSBMLHatakeyama2003 MAPK2003MODEL8256371999Mariko HatakeyamaMariko Hatakeyama, Shuhei Kimura, Takashi Naka, Takuji Kawasaki, Noriko Yumoto, Mio Ichikawa, Jae-Hoon Kim, Kazuki Saito, Mihoro Saeki, Mikako Shirouzu, Shigeyuki Yokoyama, Akihiko Konagaya12691603, ErbB tyrosine kinase receptors mediate mitogenic signal cascade by binding a variety of ligands and recruiting the different cassettes of adaptor proteins. In the present study, we examined heregulin (HRG)-induced signal transduction of ErbB4 receptor and found that the phosphatidylinositol 3'-kinase (PI3K)-Akt pathway negatively regulated the extracellular signal-regulated kinase (ERK) cascade by phosphorylating Raf-1 on Ser(259). As the time-course kinetics of Akt and ERK activities seemed to be transient and complex, we constructed a mathematical simulation model for HRG-induced ErbB4 receptor signalling to explain the dynamics of the regulation mechanism in this signal transduction cascade. The model reflected well the experimental results observed in HRG-induced ErbB4 cells and in other modes of growth hormone-induced cell signalling that involve Raf-Akt cross-talk. The model suggested that HRG signalling is regulated by protein phosphatase 2A as well as Raf-Akt cross-talk, and protein phosphatase 2A modulates the kinase activity in both the PI3K-Akt and MAPK (mitogen-activated protein kinase) pathways.. Pt 2, 373. RIKEN Genomic Sciences Center, 1-7-22 Suehirocho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. marikoh@gsc.riken.go.jpenuo.he@wolfson.ox.ac.ukUniversity of OxfordBIOMD0000000146ErbB tyrosine kinase receptors mediate mitogenic signal cascade by binding a variety of ligands and recruiting the different cassettes of adaptor proteins. In the present study, we examined heregulin (HRG)-induced signal transduction of ErbB4 receptor and found that the phosphatidylinositol 3'-kinase (PI3K)-Akt pathway negatively regulated the extracellular signal-regulated kinase (ERK) cascade by phosphorylating Raf-1 on Ser(259). As the time-course kinetics of Akt and ERK activities seemed to be transient and complex, we constructed a mathematical simulation model for HRG-induced ErbB4 receptor signalling to explain the dynamics of the regulation mechanism in this signal transduction cascade. The model reflected well the experimental results observed in HRG-induced ErbB4 cells and in other modes of growth hormone-induced cell signalling that involve Raf-Akt cross-talk. The model suggested that HRG signalling is regulated by protein phosphatase 2A as well as Raf-Akt cross-talk, and protein phosphatase 2A modulates the kinase activity in both the PI3K-Akt and MAPK (mitogen-activated protein kinase) pathways.Stimulation of isolated hepatocytes with epidermal growth factor (EGF) causes rapid tyrosine phosphorylation of the EGF receptor (EGFR) and adapter/target proteins, which was monitored with 1 and 2 s resolution at 37, 20, and 4 degrees C. The temporal responses detected for multiple signaling proteins involve both transient and sustained phosphorylation patterns, which change dramatically at low temperatures. To account quantitatively for complex responses, we employed a mechanistic kinetic model of the EGFR pathway, formulated in molecular terms as cascades of protein interactions and phosphorylation and dephosphorylation reactions. Assuming differential temperature dependencies for different reaction groups, such as SH2 and PTB domain-mediated interactions, the EGFR kinase, and the phosphatases, good quantitative agreement was obtained between computer-simulated and measured responses. The kinetic model demonstrates that, for each protein-protein interaction, the dissociation rate constant, k(off), strongly decreases at low temperatures, whereas this decline may or may not be accompanied by a large decrease in the k(on) value. Temperature-induced changes in the maximal activities of the reactions catalyzed by the EGFR kinase were moderate, compared to such changes in the V(max) of the phosphatases. However, strong changes in both the V(max) and K(m) for phosphatases resulted in moderate changes in the V(max)/K(m) ratio, comparable to the corresponding changes in EGFR kinase activity, with a single exception for the receptor phosphatase at 4 degrees C. The model suggests a significant decrease in the rates of the EGF receptor dimerization and its dephosphorylation at 4 degrees C, which can be related to the phase transition in the membrane lipids. A combination of high-resolution experimental monitoring and molecular level kinetic modeling made it possible to quantitatively account for the temperature dependence of the integrative signaling responses.A computational model on the modulation of mitogen-activated protein kinase (MAPK) and Akt pathways in heregulin-induced ErbB signalling.Temperature dependence of the epidermal growth factor receptor signaling network can be accounted for by a kinetic model.Moehren Gisela G, Markevich Nick N, Demin Oleg O, Kiyatkin Anatoly A, Goryanin Igor I, Hoek Jan B JB, Kholodenko Boris N BNHatakeyama Mariko M, Kimura Shuhei S, Naka Takashi T, Kawasaki Takuji T, Yumoto Noriko N, Ichikawa Mio M, Kim Jae-Hoon JH, Saito Kazuki K, Saeki Mihoro M, Shirouzu Mikako M, Yokoyama Shigeyuki S, Konagaya Akihiko AfalseHatakeyama2003_MAPK Figure4 and Figure5 can be simulated by Copasi. Figure4 can be simulated in MathSBML as well. There are some typos in the paper:K29=234, is it should k_29; Table2, reaction17, is there are "slash" missing in between the rate equation; reaction 33,"Akt-PI-PP" in the last term of denominator instead of "AktPI-P" . For plotting figure4, we create another extra parameter *_percent, and use assignment rule calculate percentage of each species. 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. 2024-08-212024-09-022007-09-06BIOMD00000001461269160311772030CHEBI:16618CHEBI:26034CHEBI:16152CHEBI:18367CHEBI:18361CHEBI:35782CHEBI:17552CHEBI:15996MODEL8256371999BIOMD0000000146GO:0005623GO:0006468GO:0043235GO:0005515GO:0043405GO:0051896GO:0038127GO:0005942GO:0000159GO:0005102GO:0007171GO:0004672GO:0016311GO:0004872GO:0043241GO:0032320GO:0032147GO:0006469GO:0016303GO:003162310026Q15303P15056Q9DBB1IPR015744IPR003527IPR008350IPR008349IPR002154IPR015592IPR013753IPR001452IPR000980