cross-talk and information transfer in mammalian and bacterial signaling相声和信息传递在哺乳动物和细菌的信号.pdfVIP

Cross-Talk and Information Transfer in Mammalian and Bacterial Signaling 1 1,2 Samanthe M. Lyons , Ashok Prasad * 1 School of Biomedical Engineering, Colorado State University, Fort Collins, Colorado, United States of America, 2 Chemical and Biological Engineering, Colorado State University, Fort Collins, Colorado, United States of America Abstract In mammalian and bacterial cells simple phosphorylation circuits play an important role in signaling. Bacteria have hundreds of two-component signaling systems that involve phosphotransfer between a receptor and a response regulator. In mammalian cells a similar pathway is the TGF-beta pathway, where extracellular TGF-beta ligands activate cell surface receptors that phosphorylate Smad proteins, which in turn activate many genes. In TGF-beta signaling the multiplicity of ligands begs the question as to whether cells can distinguish signals coming from different ligands, but transduced through a small set of Smads. Here we use information theory with stochastic simulations of networks to address this question. We find that when signals are transduced through only one Smad, the cell cannot distinguish between different levels of the external ligands. Increasing the number of Smads from one to two significantly improves information transmission as well as the ability to discriminate between ligands. Surprisingly, both total information transmitted and the capacity to discriminate between ligands are quite insensitive to high levels of cross-talk between the two Smads. Robustness against cross-talk requires that the average amplitude of the signals are large. We find that smaller systems, as exemplified by some two- component systems in bacteria, are significantly much less robust against cross-talk. For such sys