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2007 CompTox Forum
Abstract - Temporal Coding of ERK Signaling Network
Shinya Kuroda, M.D., Ph.D.
Professor
Graduate School of Biophysics and Biochemistry
University of Tokyo, School of Science
7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan
Phone: 81-3-5841-4697
E-mail: skuroda@bi.s.u-tokyo.ac.jp
To elucidate how epidermal growth factor (EGF) and nerve growth factor (NGF) specifically encode their distinct physical properties into transient, and transient and sustained extracellular signal-regulated kinase (ERK) activation respectively, we developed a kinetic simulation model of ERK signaling networks by constraining in silico dynamics on the basis of in vivo dynamics in PC12 cells. Measured in vivo dynamics can be consistently reproduced in dose- and temporal-dependent manners in growth factors in silico. This model allowed us to predict in silico and validate in vivo that transient ERK activation depends on rapid increases of EGF and NGF but not on their final concentrations, whereas sustained ERK activation depends on the final concentration of NGF but not on the temporal rate of increase. This system of ERK dynamics is produced by Ras and Rap1 dynamics, which capture the rapid temporal rate of growth factors and the final concentration of NGF, respectively. These results indicate that the Ras and Rap1 systems capture the temporal rate and concentration of growth factors, and encode these distinct physical properties into transient and sustained ERK activation, respectively[1]. In this symposium, I will discuss the temporal coding of ERK signaling network with our recent analysis.