Muller2008 - Simplified MAPK activation Dynamics (Model B)
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ABSTRACT:
Muller2008 - Simplified MAPK activation Dynamics (Model B)
Simplified mathematical model (model B)
for predicting MAPK signal expression.
This model is described in the article:
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 J. 2008 May; 22(5):
1393-1403
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.
SUBMITTER: 
Vijayalakshmi Chelliah
PROVIDER: BIOMD0000000664 | BioModels | 2018-01-26
REPOSITORIES: BioModels
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