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http://dx.doi.org/10.5302/J.ICROS.2004.10.12.1155

Dynamical Analysis of Cellular Signal Transduction Pathways with Nonlinear Systems Perspectives  

Kim Hyun-Woo (울산대학교 전기전자정보시스템공학부)
Cho Kwang-Hyun (서울대학교 의과대학 의학과 및 서울대학교 생명공학공동연구원)
Publication Information
Journal of Institute of Control, Robotics and Systems / v.10, no.12, 2004 , pp. 1155-1163 More about this Journal
Abstract
Extracellular signal-regulated kinase (ERK) signaling pathway is one of the mitogen-activated protein kinase (MAPK) signal transduction pathways. This pathway is known as pivotal in many signaling networks that govern proliferation, differentiation and cell survival. The ERK signaling pathway comprises positive and negative feedback loops, depending on whether the terminal kinase stimulates or inhibits the activation of the initial level. In this paper, we attempt to model the ERK pathway by considering both of the positive and negative feedback mechanisms based on Michaelis-Menten kinetics. In addition, we propose a fraction ratio model based on the mass action law. We first develop a mathematical model of the ERK pathway with fraction ratios. Secondly, we analyze the dynamical properties of the fraction ratio model based on simulation studies. Furthermore, we propose a concept of an inhibitor, catalyst, and substrate (ICS) controller which regulates the inhibitor, catalyst, and substrate concentrations of the ERK signal transduction pathway. The ICS controller can be designed through dynamical analysis of the ERK signaling transduction pathway within limited concentration ranges.
Keywords
ERK signaling pathway; fraction ratio model; nonlinear dynamics; oscillations; ICS controller;
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