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Cell Syst

Title:		Push-Pull and Feedback Mechanisms Can Align Signaling System Outputs with Inputs
Author(s):		Andrews SS; Peria WJ; Yu RC; Colman-Lerner A; Brent R;
Address:		"Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA; The Molecular Sciences Institute, Berkeley, CA 94704, USA. Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA. The Molecular Sciences Institute, Berkeley, CA 94704, USA. Instituto de Fisiologia, Biologia Molecular y Neurociencias (IFIBYNE-CONICET) and Departamento de Fisiologia, Biologia Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, C1428EHA Buenos Aires, Argentina. Division of Basic Sciences, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109, USA; The Molecular Sciences Institute, Berkeley, CA 94704, USA. Electronic address: rbrent@fhcrc.org"
Journal Title:		Cell Syst
Year:		2016
Volume:		20161027
Issue:		5
Page Number:		444 - 455
DOI:		10.1016/j.cels.2016.10.002
ISSN/ISBN:		2405-4712 (Print) 2405-4720 (Electronic) 2405-4712 (Linking)
Abstract:		"Many cell signaling systems, including the yeast pheromone response system, exhibit 'dose-response alignment' (DoRA), in which output of one or more downstream steps closely matches the fraction of occupied receptors. DoRA can improve the fidelity of transmitted dose information. Here, we searched systematically for biochemical network topologies that produced DoRA. Most networks, including many containing feedback and feedforward loops, could not produce DoRA. However, networks including 'push-pull' mechanisms, in which the active form of a signaling species stimulates downstream activity and the nominally inactive form reduces downstream activity, enabled perfect DoRA. Networks containing feedbacks enabled DoRA, but only if they also compared feedback to input and adjusted output to match. Our results establish push-pull as a non-feedback mechanism to align output with variable input and maximize information transfer in signaling systems. They also suggest genetic approaches to determine whether particular signaling systems use feedback or push-pull control"
Keywords:		"Computer Simulation Feedback, Physiological Saccharomyces cerevisiae *Signal Transduction Saccharomyces cervisiae cell signaling dose response alignment paradoxical signaling pheromone response system push-pull yeast;"
Notes:		"MedlineAndrews, Steven S Peria, William J Yu, Richard C Colman-Lerner, Alejandro Brent, Roger eng P50 HG002370/HG/NHGRI NIH HHS/ R01 GM086615/GM/NIGMS NIH HHS/ R01 GM097479/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural 2016/11/30 Cell Syst. 2016 Nov 23; 3(5):444-455.e2. doi: 10.1016/j.cels.2016.10.002. Epub 2016 Oct 27"