Muller2008 - Simplified MAPK activation Dynamics (Model B)
This model is described in the article:
Abstract:
Activation of the fibroblast growth factor (FGFR) and melanocyte stimulating hormone (MC1R) receptors stimulates B-Raf and C-Raf isoforms that regulate the dynamics of MAPK1,2 signaling. Network topology motifs in mammalian cells include feed-forward and feedback loops and bifans where signals from two upstream molecules integrate to modulate the activity of two downstream molecules. We computationally modeled and experimentally tested signal processing in the FGFR/MC1R/B-Raf/C-Raf/MAPK1,2 network in human melanoma cells; identifying 7 regulatory loops and a bifan motif. Signaling from FGFR leads to sustained activation of MAPK1,2, whereas signaling from MC1R results in transient activation of MAPK1,2. The dynamics of MAPK activation depends critically on the expression level and connectivity to C-Raf, which is critical for a sustained MAPK1,2 response. A partially incoherent bifan motif with a feedback loop acts as a logic gate to integrate signals and regulate duration of activation of the MAPK signaling cascade. Further reducing a 106-node ordinary differential equations network encompassing the complete network to a 6-node network encompassing rate-limiting processes sustains the feedback loops and the bifan, providing sufficient information to predict biological responses.
This model is hosted on BioModels Database and identified by: BIOMD0000000664.
To cite BioModels Database, please use: Chelliah V et al. BioModels: ten-year anniversary. Nucl. Acids Res. 2015, 43(Database issue):D542-8.
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.
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Network topology determines dynamics of the mammalian MAPK1,2 signaling network: bifan motif regulation of C-Raf and B-Raf isoforms by FGFR and MC1R.
- Muller M, Obeyesekere M, Mills GB, Ram PT
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology , 5/ 2008 , Volume 22 , Issue 5 , pages: 1393-1403 , PubMed ID: 18171696
- Department of Systems Biology, UT M.D. Anderson Cancer Center, 7435 Fannin St., Houston, TX 77054, USA.
- Activation of the fibroblast growth factor (FGFR) and melanocyte stimulating hormone (MC1R) receptors stimulates B-Raf and C-Raf isoforms that regulate the dynamics of MAPK1,2 signaling. Network topology motifs in mammalian cells include feed-forward and feedback loops and bifans where signals from two upstream molecules integrate to modulate the activity of two downstream molecules. We computationally modeled and experimentally tested signal processing in the FGFR/MC1R/B-Raf/C-Raf/MAPK1,2 network in human melanoma cells; identifying 7 regulatory loops and a bifan motif. Signaling from FGFR leads to sustained activation of MAPK1,2, whereas signaling from MC1R results in transient activation of MAPK1,2. The dynamics of MAPK activation depends critically on the expression level and connectivity to C-Raf, which is critical for a sustained MAPK1,2 response. A partially incoherent bifan motif with a feedback loop acts as a logic gate to integrate signals and regulate duration of activation of the MAPK signaling cascade. Further reducing a 106-node ordinary differential equations network encompassing the complete network to a 6-node network encompassing rate-limiting processes sustains the feedback loops and the bifan, providing sufficient information to predict biological responses.
Submitter of this revision: administrator
Modellers: administrator, Vijayalakshmi Chelliah
Metadata information
isDescribedBy (1 statement)
hasTaxon (1 statement)
hasProperty (2 statements)
Gene Ontology regulation of MAPK cascade
occursIn (1 statement)
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| BIOMD0000000664_urn.xml | Auto-generated SBML file with URNs | 73.57 KB | Preview | Download |
| MODEL8687732743.cps | COPASI file | 94.16 KB | Preview | Download |
| MODEL8687732743.sedml | File for figure 4b. To generate figures 2b and 2c, adjust g1 and g2 parameter value expressions accordingly. | 1.65 KB | Preview | Download |
- Model originally submitted by : Vijayalakshmi Chelliah
- Submitted: Apr 23, 2009 2:17:41 PM
- Last Modified: Jan 29, 2018 12:55:14 PM
Revisions
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Version: 3
- Submitted on: Jan 29, 2018 12:55:14 PM
- Submitted by: administrator
- With comment: Model name updated using online editor.
-
Version: 2
- Submitted on: Apr 23, 2009 2:17:41 PM
- Submitted by: Vijayalakshmi Chelliah
- With comment: Current version of Muller2008_MAPKactivation_Dynamics
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Version: 1
- Submitted on: Apr 23, 2009 2:17:41 PM
- Submitted by: Vijayalakshmi Chelliah
- With comment: Original import of Muller2008_MAPKactivation_Dynamics
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: Variable used inside SBML models
| Species | Initial Concentration/Amount |
|---|---|
| C Raf RAF proto-oncogene serine/threonine-protein kinase |
0.0 mol |
| FGFR Fibroblast growth factor receptor 1 |
0.0 mol |
| MSH melanocyte-stimulating hormone receptor |
0.0 mol |
| B Raf Serine/threonine-protein kinase B-raf |
0.0 mol |
| g1 0 Fibroblast growth factor 1 ; Stimulus |
0.0 mol |
| MAPK Mitogen-activated protein kinase 1 |
0.0 mol |
| Reactions | Rate | Parameters |
|---|---|---|
| C_Raf => C_Raf_inactive; MSH | Compartment*h36_y3*MSH*C_Raf | h36_y3 = 0.1 0.06*ml/(mol*s) |
| FGFR => | Compartment*d1*FGFR | d1 = 0.2 1/(59.9999*s) |
| => MSH; g2_0 | Compartment*a2*g2/(b2+g2) | b2 = 10.0; a2 = 10.0 0.06*mmol/(l*s); g2 = 1.0 |
| MSH => | Compartment*d2*MSH | d2 = 0.1 1/(59.9999*s) |
| => FGFR; g1_0 | Compartment*a1*g1/(b1+g1) | b1 = 10.0; a1 = 10.0 0.06*mmol/(l*s); g1 = 0.0 |
| => B_Raf; MSH | Compartment*f24*MSH | f24 = 0.8 1/(59.9999*s) |
| => C_Raf; C_Raf_inactive, MAPK | Compartment*f53*((E-C_Raf)-C_Raf_inactive)*MAPK | E = 10.0; f53 = 1.5 0.06*ml/(mol*s) |
| g1_0 = g1 | [] | g1 = 0.0 |
| MAPK => | Compartment*d5*MAPK | d5 = 1.0 1/(59.9999*s) |
| => B_Raf; FGFR | Compartment*f14*FGFR | f14 = 0.1 1/(59.9999*s) |
(added: 29 Jan 2018, 12:41:59, updated: 29 Jan 2018, 12:41:59)