The Mitogen-Activated Protein Kinase (MAPK) Cascade
James
Lawson
Auckland Bioengineering Institute, The University of Auckland
Model Status
This CellML model runs in both OpenCell and COR to reproduce the results given by running the Mathematica description of the model (provided by the original model author) using the Mathematica NDSolve integration algorithm. The units have been checked and they are consistent.
Model Structure
ABSTRACT: The mitogen-activated protein kinase (MAPK) cascade is a highly conserved series of three protein kinases implicated in diverse biological processes. Here we demonstrate that the cascade arrangement has unexpected consequences for the dynamics of MAPK signaling. We solved the rate equations for the cascade numerically and found that MAPK is predicted to behave like a highly cooperative enzyme, even though it was not assumed that any of the enzymes in the cascade were regulated cooperatively. Measurements of MAPK activation in Xenopus oocyte extracts confirmed this prediction. The stimulus/response curve of the MAPK was found to be as steep as that of a cooperative enzyme with a Hill coefficient of 4-5, well in excess of that of the classical allosteric protein hemoglobin. The shape of the MAPK stimulus/ response curve may make the cascade particularly appropriate for mediating processes like mitogenesis, cell fate induction, and oocyte maturation, where a cell switches from one discrete state to another.
The original paper reference is cited below:
Ultrasensitivity in the mitogen-activated protein cascade, Chi-Ying F. Huang and James E. Ferrell, Jr., 1996, Proc. Natl. Acad. Sci. USA
, 93, 10078-10083. PubMed ID: 8816754
the conventional rendering of the MAPK cascade
Schematic diagram of the MAPK cascade described by the model.
mos
MAPKKK
mose1
MAPKKK-E1 complex
mosstar
activated MAPKKK
mosstare2
activated MAPKKK-E2 complex
mek
MAPKK
mekmosstar
MAPKK-activated MAPKKK complex
mekstar
phosphorylated MAPKK
mekstarmekpase
phopsphorylated MAPKK-MAPKK phosphorylase complex
mekstarmosstar
phosphorylated MAPKK-activated MAPKKK complex
mekstarstar
biphosphorylated MAPKK
mekstarstarmekpase
biphosphorylated MAPKK-MAPKK phosphatase complex
mapk
MAPK
mapkmekstarstar
MAPK-biphosphorylated MAPKK complex
mapkstar
phosphorylated MAPK
mapkstarmekstarstar
phosphorylated MAPK-biphosphorylated MAPKK complex
mapkstarstar
biphosphorylated MAPK
mapkstarmapkpase
phosphorylated MAPK-MAPK phosphatase complex
mapkstarstarmapkpase
biphosphorylated MAPK-MAPK phosphatase complex
This model has been rebuilt using the differential rate equations that Ferrel et al. use in their paper to describe the signalling pathway. This model is able to reproduce precisely the same output as that given by running the Mathematica description of the model (provided by the author) using the Mathematica NDSolve integration algorithm. This version of the model runs in both PCEnv (0.2+) and COR.
Ultrasensitivity in the mitogen-activated protein kinase cascade
93
10078
10083
James
Ferrell
E
James Lawson
1996-09-17 00:00
James Lawson
50
Proceedings of the National Academy of Science, USA
j.lawson@auckland.ac.nz
2007-10-23T00:00:00+00:00
The University of Auckland
Auckland Bioengineering Institute
Bioengineering Institute
keyword
MAPK
signal transduction
oocyte
James
Lawson
Richard
This is the CellML description of Huang and Ferrell's mathematical model of the mitogen-activated protein kinase (MAPK) cascade (1996). This signalling pathway involves a series of three, highly conserved protein kinases which are associated with a diverse array of biological responses.
Chi-Ying
Huang
F
8816754
100