TAILIEUCHUNG - Báo cáo khoa học: Regulating the total level of a signaling protein can vary its dynamics in a range from switch like ultrasensitivity to adaptive responses

Biological signaling networks can exhibit rich response dynamics including ultrasensitivity, adaptation to persistent stimuli and oscillations. Previous modeling efforts have considered the proteins in these networks as two-state entities and their total levels as fixed quantities. | ễFEBS Journal Regulating the total level of a signaling protein can vary its dynamics in a range from switch like ultrasensitivity to adaptive responses Orkun S. Soyer Hiroyuki Kuwahara and Attila Csikasz-Nagy Microsoft Research - University of Trento Centre for Computationaland Systems Biology Italy Keywords adaptation modeling signaling signal-response curve ultrasensitivity Correspondence O. S. Soyer and A. Csikasz-Nagy CoSBi Piazza Manci 17 Povo TN 38100 Italy Fax 39 0461 882814 Tel 39 0461 882823 39 0461 882824 E-mail soyer@ csikasz@ Website http Note The mathematical model described here has been submitted to the Online Cellular Systems Modelling Database and can be accessed free of charge at http jjj. database soyer Received 11 February 2009 revised 17 March 2009 accepted 7 April2009 doi Biological signaling networks can exhibit rich response dynamics including ultrasensitivity adaptation to persistent stimuli and oscillations. Previous modeling efforts have considered the proteins in these networks as two-state entities and their total levels as fixed quantities. However inside the cell most molecules are in constant flux because of various processes such as degradation synthesis binding of scaffold proteins and release from vesicles. The resulting freedom in the amount of signaling protein that is available for signaling has not been explored. Here we analyze the response dynamics of a signaling protein when it enters the signaling pool in one state modified or unmodified and exits in both states. When the exit rates of these two states are comparable a persistent stimulus results in step responses and can produce ultrasensitivity as shown previously. However we find that when the exit rates are imbalanced the signaling protein gives transient responses to persistent stimuli even though the system does not have any explicit feedback. Further these rates determine the

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