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    Science. 2005 Aug 12;309(5737):1078-83.

    Formation of regulatory patterns during signal propagation in a Mammalian cellular network.

    Ma'ayan A, Jenkins SL, Neves S, Hasseldine A, Grace E, Dubin-Thaler B, Eungdamrong NJ, Weng G, Ram PT, Rice JJ, Kershenbaum A, Stolovitzky GA, Blitzer RD, Iyengar R.

    Department of Pharmacology and Biological Chemistry Mount Sinai School of Medicine, New York, NY 10029, USA.

    We developed a model of 545 components (nodes) and 1259 interactions representing signaling pathways and cellular machines in the hippocampal CA1 neuron. Using graph theory methods, we analyzed ligand-induced signal flow through the system. Specification of input and output nodes allowed us to identify functional modules. Networking resulted in the emergence of regulatory motifs, such as positive and negative feedback and feedforward loops, that process information. Key regulators of plasticity were highly connected nodes required for the formation of regulatory motifs, indicating the potential importance of such motifs in determining cellular choices between homeostasis and plasticity.

    PMID: 16099987 [PubMed - indexed for MEDLINE]

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