Levchenko2000_MAPK_noScaffold
Model Identifier
BIOMD0000000011
Short description
MAPK cascade in solution (no scaffold)
| Description |
|---|
| This model describes a basic 3- stage Mitogen Activated Protein Kinase (MAPK) cascade in solution. This cascade is typically expressed as RAF= =>MEK==>MAPK (alternative forms are K3==>K2==> K1 and KKK==>KK==>K) . The input signal is RAFK (RAF Kinase) and the output signal is MAPKpp ( doubly phosphorylated form of MAPK) . RAFK phosphorylates RAF once to RAFp. RAFp, the phosphorylated form of RAF induces two phoshporylations of MEK, to MEKp and MEKpp. MEKpp, the doubly phosphorylated form of MEK, induces two phosphorylations of MAPK to MAPKp and MAPKpp. |
| Rate constant | Reaction |
|---|---|
| a10 = 5. | MAPKPH + MAPKpp -> MAPKppMAPKPH |
| a1 = 1. | RAF + RAFK -> RAFRAFK |
| a2 = 0.5 | RAFp + RAFPH -> RAFpRAFPH |
| a3 = 3.3 | MEK + RAFp -> MEKRAFp |
| a4 = 10. | MEKp + MEKPH -> MEKpMEKPH |
| a5 = 3.3 | MEKp + RAFp -> MEKpRAFp |
| a6 = 10. | MEKPH + MEKpp -> MEKppMEKPH |
| a7 = 20. | MAPK + MEKpp -> MAPKMEKpp |
| a8 = 5. | MAPKp + MAPKPH -> MAPKpMAPKPH |
| a9 = 20. | MAPKp + MEKpp -> MAPKpMEKpp |
| d10 = 0.4 | MAPKppMAPKPH -> MAPKPH + MAPKpp |
| d1 = 0.4 | RAFRAFK -> RAF + RAFK |
| d2 = 0.5 | RAFpRAFPH -> RAFp + RAFPH |
| d3 = 0.42 | MEKRAFp -> MEK + RAFp |
| d4 = 0.8 | MEKpMEKPH -> MEKp + MEKPH |
| d5 = 0.4 | MEKpRAFp -> MEKp + RAFp |
| d6 = 0.8 | MEKppMEKPH -> MEKPH + MEKpp |
| d7 = 0.6 | MAPKMEKpp -> MAPK + MEKpp |
| d8 = 0.4 | MAPKpMAPKPH -> MAPKp + MAPKPH |
| d9 = 0.6 | MAPKpMEKpp -> MAPKp + MEKpp |
| k10 = 0.1 | MAPKppMAPKPH -> MAPKp + MAPKPH |
| k1 = 0.1 | RAFRAFK -> RAFK + RAFp |
| k2 = 0.1 | RAFpRAFPH -> RAF + RAFPH |
| k3 = 0.1 | MEKRAFp -> MEKp + RAFp |
| k4 = 0.1 | MEKpMEKPH -> MEK + MEKPH |
| k5 = 0.1 | MEKpRAFp -> MEKpp + RAFp |
| k6 = 0.1 | MEKppMEKPH -> MEKp + MEKPH |
| k7 = 0.1 | MAPKMEKpp -> MAPKp + MEKpp |
| k8 = 0.1 | MAPKpMAPKPH -> MAPK + MAPKPH |
| k9 = 0.1 | MAPKpMEKpp -> MAPKpp + MEKpp |
| Variable | IC | ODE |
|---|---|---|
| MAPK | 0.3 | MAPK'[t] == d7*MAPKMEKpp[t] + k8*MAPKpMAPKPH[t] - a7*MAPK[t]*MEKpp[t] |
| MAPKMEKpp | 0 | MAPKMEKpp'[t] == -(d7*MAPKMEKpp[t]) - k7*MAPKMEKpp[t] + a7*MAPK[t]*MEKpp[t] |
| MAPKp | 0 | MAPKp'[t] == k7*MAPKMEKpp[t] - a8*MAPKp[t]*MAPKPH[t] + d8*MAPKpMAPKPH[t] + d9*MAPKpMEKpp[t] + k10* MAPKppMAPKPH[t] - a9*MAPKp[t]*MEKpp[t] |
| MAPKPH | 0.3 | MAPKPH'[t] == -(a8*MAPKp[t]*MAPKPH[t]) + d8*MAPKpMAPKPH[ t] + k8*MAPKpMAPKPH[t] - a10*MAPKPH[t]*MAPKpp[t] + d10*MAPKppMAPKPH[t] + k10*MAPKppMAPKPH[t] |
| MAPKpMAPKPH | 0 | MAPKpMAPKPH'[t] == a8*MAPKp[t]*MAPKPH[t] - d8* MAPKpMAPKPH[t] - k8*MAPKpMAPKPH[t] |
| MAPKpMEKpp | 0 | MAPKpMEKpp'[t] == -(d9*MAPKpMEKpp[t]) - k9*MAPKpMEKpp[t] + a9*MAPKp[t]*MEKpp[t] |
| MAPKpp | 0 | MAPKpp'[t] == k9*MAPKpMEKpp[t] - a10*MAPKPH[t]*MAPKpp[t] + d10*MAPKppMAPKPH[t] |
| MAPKppMAPKPH | 0 | MAPKppMAPKPH'[t] == a10*MAPKPH[t]*MAPKpp[t] - d10* MAPKppMAPKPH[t] - k10*MAPKppMAPKPH[t] |
| MEK | 0.2 | MEK'[t] == k4*MEKpMEKPH[t] + d3*MEKRAFp[t] - a3*MEK[t]*RAFp[t] |
| MEKp | 0 | MEKp'[t] == -(a4*MEKp[t]*MEKPH[t]) + d4*MEKpMEKPH[t] + k6*MEKppMEKPH[t] + d5*MEKpRAFp[t] + k3*MEKRAFp[ t] - a5*MEKp[t]*RAFp[t] |
| MEKPH | 0.2 | MEKPH'[t] == -(a4*MEKp[t]*MEKPH[t]) + d4*MEKpMEKPH[t] + k4*MEKpMEKPH[t] - a6*MEKPH[t]*MEKpp[t] + d6* MEKppMEKPH[t] + k6*MEKppMEKPH[t] |
| MEKpMEKPH | 0 | MEKpMEKPH'[t] == a4*MEKp[t]*MEKPH[t] - d4*MEKpMEKPH[t] - k4*MEKpMEKPH[t] |
| MEKpp | 0 | MEKpp'[t] == d7*MAPKMEKpp[t] + k7*MAPKMEKpp[t] + d9*MAPKpMEKpp[t] + k9*MAPKpMEKpp[t] - a7*MAPK[t]* MEKpp[t] - a9*MAPKp[t]*MEKpp[t] - a6*MEKPH[t]*MEKpp[t] + d6*MEKppMEKPH[t] + k5*MEKpRAFp[t] |
| MEKppMEKPH | 0 | MEKppMEKPH'[t] == a6*MEKPH[t]*MEKpp[t] - d6*MEKppMEKPH[ t] - k6*MEKppMEKPH[t] |
| MEKpRAFp | 0 | MEKpRAFp'[t] == -(d5*MEKpRAFp[t]) - k5*MEKpRAFp[t] + a5*MEKp[t]*RAFp[t] |
| MEKRAFp | 0 | MEKRAFp'[t] == -(d3*MEKRAFp[t]) - k3*MEKRAFp[t] + a3*MEK[t]*RAFp[t] |
| RAF | 0.4 | RAF'[t] == -(a1*RAF[t]*RAFK[t]) + k2*RAFpRAFPH[t] + d1*RAFRAFK[t] |
| RAFK | 0.1 | RAFK'[t] == -(a1*RAF[t]*RAFK[t]) + d1*RAFRAFK[t] + k1*RAFRAFK[t] |
| RAFp | 0 | RAFp'[t] == d5*MEKpRAFp[t] + k5*MEKpRAFp[t] + d3*MEKRAFp[t] + k3*MEKRAFp[t] - a3*MEK[t]*RAFp[t] - a5*MEKp[t]*RAFp[t] - a2*RAFp[t]*RAFPH[t] + d2* RAFpRAFPH[t] + k1*RAFRAFK[t] |
| RAFPH | 0.3 | RAFPH'[t] == -(a2*RAFp[t]*RAFPH[t]) + d2*RAFpRAFPH[t] + k2*RAFpRAFPH[t] |
| RAFpRAFPH | 0 | RAFpRAFPH'[t] == a2*RAFp[t]*RAFPH[t] - d2*RAFpRAFPH[t] - k2*RAFpRAFPH[t] |
| RAFRAFK | 0 | RAFRAFK'[t] == a1*RAF[t]*RAFK[t] - d1*RAFRAFK[t] - k1*RAFRAFK[t] |
Generated by Cellerator Version 1.4.3 (6-March-2004) using Mathematica 5.0 for Mac OS X (November 19, 2003), March 6, 2004 12:18:07, using (PowerMac, PowerPC,Mac OS X,MacOSX,Darwin)
author=B.E.Shapiro
This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2010 The BioModels.net Team.
For more information see the terms of use
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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
-
Scaffold proteins may biphasically affect the levels of mitogen-activated protein kinase signaling and reduce its threshold properties.
- Levchenko A, Bruck J, Sternberg PW
- Proceedings of the National Academy of Sciences of the United States of America , 5/ 2000 , Volume 97 , pages: 5818-5823 , PubMed ID: 10823939
- Division of Engineering and Applied Science and Division of Biology and Howard Hughes Medical Institute, California Institute of Technology, Pasadena, CA 91125, USA. andre@paradise.caltech.edu
- In addition to preventing crosstalk among related signaling pathways, scaffold proteins might facilitate signal transduction by preforming multimolecular complexes that can be rapidly activated by incoming signal. In many cases, such as mitogen-activated protein kinase (MAPK) cascades, scaffold proteins are necessary for full activation of a signaling pathway. To date, however, no detailed biochemical model of scaffold action has been suggested. Here we describe a quantitative computer model of MAPK cascade with a generic scaffold protein. Analysis of this model reveals that formation of scaffold-kinase complexes can be used effectively to regulate the specificity, efficiency, and amplitude of signal propagation. In particular, for any generic scaffold there exists a concentration value optimal for signal amplitude. The location of the optimum is determined by the concentrations of the kinases rather than their binding constants and in this way is scaffold independent. This effect and the alteration of threshold properties of the signal propagation at high scaffold concentrations might alter local signaling properties at different subcellular compartments. Different scaffold levels and types might then confer specialized properties to tune evolutionarily conserved signaling modules to specific cellular contexts.
Contributors
Submitter of the first revision: Nicolas Le Novère
Submitter of this revision: Nicolas Le Novère
Modellers: Nicolas Le Novère
Submitter of this revision: Nicolas Le Novère
Modellers: Nicolas Le Novère
Metadata information
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isDescribedBy (1 statement)
isDerivedFrom (3 statements)
hasTaxon (1 statement)
isVersionOf (1 statement)
isHomologTo (1 statement)
isDescribedBy (1 statement)
isDerivedFrom (3 statements)
hasTaxon (1 statement)
isVersionOf (1 statement)
isHomologTo (1 statement)
Curation status
Curated
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Connected external resources
SBGN view in Newt Editor
| Name | Description | Size | Actions |
|---|---|---|---|
Model files |
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| BIOMD0000000011_url.xml | SBML L2V4 representation of Levchenko2000_MAPK_noScaffold | 73.50 KB | Preview | Download |
Additional files |
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| BIOMD0000000011-biopax2.owl | Auto-generated BioPAX (Level 2) | 62.17 KB | Preview | Download |
| BIOMD0000000011-biopax3.owl | Auto-generated BioPAX (Level 3) | 102.48 KB | Preview | Download |
| BIOMD0000000011.m | Auto-generated Octave file | 12.55 KB | Preview | Download |
| BIOMD0000000011.pdf | Auto-generated PDF file | 280.67 KB | Preview | Download |
| BIOMD0000000011.png | Auto-generated Reaction graph (PNG) | 193.28 KB | Preview | Download |
| BIOMD0000000011.sci | Auto-generated Scilab file | 8.57 KB | Preview | Download |
| BIOMD0000000011.svg | Auto-generated Reaction graph (SVG) | 77.41 KB | Preview | Download |
| BIOMD0000000011.vcml | Auto-generated VCML file | 108.97 KB | Preview | Download |
| BIOMD0000000011.xpp | Auto-generated XPP file | 8.98 KB | Preview | Download |
| BIOMD0000000011_manual.png | Manually generated Reaction graph (PNG) | 193.28 KB | Preview | Download |
| BIOMD0000000011_manual.svg | Manually generated Reaction graph (SVG) | 77.41 KB | Preview | Download |
| BIOMD0000000011_urn.xml | Auto-generated SBML file with URNs | 78.07 KB | Preview | Download |
- Model originally submitted by : Nicolas Le Novère
- Submitted: Sep 13, 2005 1:41:40 PM
- Last Modified: Jun 3, 2013 2:36:09 PM
Revisions
-
Version: 2
- Submitted on: Jun 3, 2013 2:36:09 PM
- Submitted by: Nicolas Le Novère
- With comment: Current version of Levchenko2000_MAPK_noScaffold
-
Version: 1
- Submitted on: Sep 13, 2005 1:41:40 PM
- Submitted by: Nicolas Le Novère
- With comment: Original import of Levchenko2000_MAPK_noScaffold
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Legends
: Variable used inside SBML models
: Variable used inside SBML models
Species
| Species | Initial Concentration/Amount |
|---|---|
| MAPKpMAPKPH Mitogen-activated protein kinase 1 ; Dual specificity protein phosphatase 1-B |
0.0 μmol |
| MEKpRAFp RAF proto-oncogene serine/threonine-protein kinase ; Dual specificity mitogen-activated protein kinase kinase 1 |
0.0 μmol |
| RAF RAF proto-oncogene serine/threonine-protein kinase |
0.3 μmol |
| MAPK Mitogen-activated protein kinase 1 |
0.4 μmol |
| MAPKMEKpp Mitogen-activated protein kinase 1 ; Dual specificity mitogen-activated protein kinase kinase 1 |
0.0 μmol |
| MEKPH | 0.2 μmol |
| MEKp Dual specificity mitogen-activated protein kinase kinase 1 |
0.0 μmol |
| MAPKpp Mitogen-activated protein kinase 1 |
0.0 μmol |
| MEKpp Dual specificity mitogen-activated protein kinase kinase 1 |
0.0 μmol |
Reactions
| Reactions | Rate | Parameters |
|---|---|---|
| MAPKp + MAPKPH => MAPKpMAPKPH | a8*MAPKp*MAPKPH | a8=5.0 |
| MEKpRAFp => MEKpp + RAFp | k5*MEKpRAFp | k5=0.1 |
| RAF + RAFK => RAFRAFK | a1*RAF*RAFK | a1=1.0 |
| MAPKpMAPKPH => MAPK + MAPKPH | k8*MAPKpMAPKPH | k8=0.1 |
| MAPK + MEKpp => MAPKMEKpp | a7*MAPK*MEKpp | a7=20.0 |
| MEKp + MEKPH => MEKpMEKPH | a4*MEKp*MEKPH | a4=10.0 |
| MEKp + RAFp => MEKpRAFp | a5*MEKp*RAFp | a5=3.3 |
| RAFRAFK => RAF + RAFK | d1*RAFRAFK | d1=0.4 |
| MAPKppMAPKPH => MAPKPH + MAPKpp | d10*MAPKppMAPKPH | d10=0.4 |
| MAPKMEKpp => MAPKp + MEKpp | k7*MAPKMEKpp | k7=0.1 |
Curator's comment:
(added: 26 Nov 2010, 04:31:48, updated: 26 Nov 2010, 04:31:48)
(added: 26 Nov 2010, 04:31:48, updated: 26 Nov 2010, 04:31:48)
Reproduction of the signal-response curve of the model without scaffolding from figure 2 C. The calculations were performed using the parameter scan task of Copasi 4.6. The initial concentration of RAFK was varied from 0 to 2 uM with 100 intervals and a time course run over 100 sec at each. The concentration of MAPK-PP was integrated over the range of the whole time course.