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Originally published as Biophys J. BioFAST on September 28, 2004.
doi:10.1529/biophysj.104.051888
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Biophysical Journal 87:L01-L02 (2004)
© 2004 The Biophysical Society

MAPK Cascade Possesses Decoupled Controllability of Signal Amplification and Duration

Kapil Mayawala, Claudio A. Gelmi and Jeremy S. Edwards

Department of Chemical Engineering, University of Delaware, Newark, Delaware 19716

Correspondence: Address reprint requests and inquiries to Jeremy S. Edwards, Tel.: 302-831-8072; Fax: 302-831-1048; E-mail: edwards{at}che.udel.edu.

The three important characteristics of the output signal of mitogen activated protein kinase (MAPK) cascade are time delay between stimulus and response, amplitude gain, and duration of the output signal. In this study, we performed a sensitivity analysis on the computational model of epidermal growth factor receptor (EGFR) activated MAPK cascade developed by Schoeberl and co-workers (1) to identify the sensitive steps of the pathway affecting these characteristics. We show that the signaling network is sensitive in a decoupled manner, which provides the ability to control its output amplitude and duration one at a time. Signal duration is found sensitive only to the phosphatase reactions at the MEK level. In contrast, signal amplitude is found most sensitive to the phosphatase reactions at the ERK level. Time delay is found to be a robust characteristic of the system.




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Copyright © 2004 by the Biophysical Society.