Copyright © 2012 Vilda Purutçuoğlu and Ernst Wit. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
The MAPK/ERK pathway is a major signal transduction system
which regulates many fundamental cellular processes including the
growth control and the cell death. As a result of these roles, it has
a crucial importance in cancer as well as normal developmental processes.
Therefore, it has been intensively studied resulting in a wealth
of knowledge about its activation. It is also well documented that
the activation kinetics of the pathway is crucial to determine the nature
of the biological response. However, while individual biochemical
steps are well characterized, it is still difficult to predict or even understand
how the activation kinetics works. The aim of this paper is to
estimate the stochastic rate constants of the MAPK/ERK network dynamics.
Accordingly, taking a Bayesian approach, we combined underlying
qualitative biological knowledge in several competing dynamic
models via sets of quasireactions and estimated the stochastic rate constants
of these reactions. Comparing the resulting estimates via the
BIC and DIC criteria, we chose a biological model which includes
EGFR degradation—Raf-MEK-ERK cascade without the involvement
of RKIPs.