Intracellular signal transduction pathways are routes of information communication allowing living cells to scan their environment and internal state and respond appropriately to various stimuli. This function, as well as the details of the underlying biochemistry, suggest that quantification and analysis of information passed and processed by signaling pathways might represent a convenient and informative framework for the analysis the signaling pathway structure and of the sensitivity of signaling response. Here we propose to develop an information theory based analysis of information transfer and processing in signal transduction pathways with a specific emphasis on the MAPK and NF-kappaB pathways. We propose to combine the results of mathematical, computational and experimental studies of these pathways with development of an information theoretical treatment of information flow through biochemical reactions and/or groups of reactions (signaling modules). A set of preliminary results suggest that the development of this theory is feasible and can lead to a series of interesting and important insights about cell signaling. We propose that the amount of information transmitted in signaling pathways can be estimated in the usual units (bits per unit time) leading to clear definitions of channel capacity, redundancy, information coding and noise resistance. We propose how these notions can be applied to two specific and vitally important signal transduction pathways, where the information flow is dynamic and may be regulated in a spatially distributed and/or feedback fashion. In summary, we propose to develop a mathematical information theory of signal transduction in living cells as a theoretical analysis framework distinct from and complementary to the more traditional mathematical and computational approaches. ? ?
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