tailieunhanh - Báo cáo khoa học: Quantitative analysis of ultrasensitive responses

Ultrasensitive responses are common in cellular information transfer because they allow cells to decode extracellular stimuli in an all-or-none manner. Biochemical responses are usually analyzed by fitting the Hill equation, and the estimated Hill coefficient is taken as a measure of sensi-tivity. However, this approach is not appropriate if the response under con-sideration significantly deviates from the best-fit Hill equation. | ềFEBS Journal Quantitative analysis of ultrasensitive responses Stefan Legewie Nils Bluthgen and Hanspeter Herzel Institute for TheoreticalBiology Humboldt University Berlin Germany Keywords basalactivation Hill coefficient metabolic control analysis response coefficient ultrasensitivity Correspondence S. Legewie Institute for TheoreticalBiology Humboldt University Berlin Invalidenstrasse 43 Berlin D-10115 Germany Fax 49 30 20938801 Tel 49 30 20938496 E-mail Received 23 March 2005 revised 7 June 2005 accepted 14 June 2005 doi Ultrasensitive responses are common in cellular information transfer because they allow cells to decode extracellular stimuli in an all-or-none manner. Biochemical responses are usually analyzed by fitting the Hill equation and the estimated Hill coefficient is taken as a measure of sensitivity. However this approach is not appropriate if the response under consideration significantly deviates from the best-fit Hill equation. In addition Hill coefficients greater than unity do not necessarily imply ultrasensitive behaviour if basal activation is significant. In order to circumvent these problems we propose a general method for the quantitative analysis of sensitivity the relative amplification plot which is based on the response coefficient defined in metabolic control analysis. To quantify sensitivity globally . over the whole stimulus range we introduce the integral-based relative amplification coefficient. Our relative amplification approach can easily be extended to monotonically decreasing bell-shaped or nonsaturated responses. In cellular signal transduction a stimulus . an extracellular hormone brings about intracellular responses such as transcription. These responses may depend on the extracellular hormone concentration in a gradual or an ultrasensitive . all-or-none manner. In gradual systems a large relative increase in the stimulus is required to accomplish .

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