Bidirectional information transfer in intracellular signaling: theory and experiments
by
Alejandra C Ventura
University of Michigan, Internal Medicine Hematology/Oncology and Comprehensive Cancer Center
Coauthors: Jacques-A Sepulchre, Lauren McNeil, Peng Jiang, Alexander Ninfa, Sofia D Merajver

In this study we characterize the information flow in signal transduction networks composed of cycles of covalent modification of proteins.

We have shown recently by modeling that signaling systems that transmit information by means of a succession of covalent modifications cycles —the ubiquitous signaling cascade— can exhibit bidirectional signal propagation [1]. This result challenges the widespread notion of unidirectional signal flow and has broad implications for our understanding of cell signaling.

We have now quantified experimentally the bidirectional transfer of information in purified bicyclic cascades that mediate nitrogen regulation in E. coli, elucidated the mechanisms for this information flow by means of a dual experimental-theoretical approach, and integrated this information into models of the nitrogen-regulatory system.

Reverse propagation is likely to be a general phenomenon in bioscience and it is expected that our results will provoke reinterpretation of previous data. Bidirectional propagation might be advantageous in some systems and not in others; we hypothesize that systems have evolved mechanisms to control this backwards propagation and thus to reveal and characterize these regulatory mechanisms is within our goals. This could have critical implications in matching the biological behavior of cells with the underlying signaling circuit.

[1] Ventura A, Sepulchre J-A, Merajver S (2008) A hidden feedback in signaling cascades is revealed. PLoS Comput. Biol. 4(3): e1000041.

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Date received: May 12, 2008