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Mol Biol Cell

Title:		Combined computational and experimental analysis reveals mitogen-activated protein kinase-mediated feedback phosphorylation as a mechanism for signaling specificity
Author(s):		Hao N; Yildirim N; Nagiec MJ; Parnell SC; Errede B; Dohlman HG; Elston TC;
Address:		"Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"
Journal Title:		Mol Biol Cell
Year:		2012
Volume:		20120808
Issue:		19
Page Number:		3899 - 3910
DOI:		10.1091/mbc.E12-04-0333
ISSN/ISBN:		1939-4586 (Electronic) 1059-1524 (Print) 1059-1524 (Linking)
Abstract:		"Different environmental stimuli often use the same set of signaling proteins to achieve very different physiological outcomes. The mating and invasive growth pathways in yeast each employ a mitogen-activated protein (MAP) kinase cascade that includes Ste20, Ste11, and Ste7. Whereas proper mating requires Ste7 activation of the MAP kinase Fus3, invasive growth requires activation of the alternate MAP kinase Kss1. To determine how MAP kinase specificity is achieved, we used a series of mathematical models to quantitatively characterize pheromone-stimulated kinase activation. In accordance with the computational analysis, MAP kinase feedback phosphorylation of Ste7 results in diminished activation of Kss1, but not Fus3. These findings reveal how feedback phosphorylation of a common pathway component can limit the activity of a competing MAP kinase through feedback phosphorylation of a common activator, and thereby promote signal fidelity"
Keywords:		"Algorithms Computer Simulation *Feedback, Physiological *MAP Kinase Signaling System Mitogen-Activated Protein Kinase Kinases/metabolism Mitogen-Activated Protein Kinases/metabolism *Models, Biological Monte Carlo Method Nonlinear Dynamics Phosphorylation;"
Notes:		"MedlineHao, Nan Yildirim, Necmettin Nagiec, Michal J Parnell, Stephen C Errede, Beverly Dohlman, Henrik G Elston, Timothy C eng GM073180/GM/NIGMS NIH HHS/ GM084071/GM/NIGMS NIH HHS/ R01 GM084071/GM/NIGMS NIH HHS/ R01 GM073180/GM/NIGMS NIH HHS/ GM079271/GM/NIGMS NIH HHS/ R01 GM079271/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural 2012/08/10 Mol Biol Cell. 2012 Oct; 23(19):3899-910. doi: 10.1091/mbc.E12-04-0333. Epub 2012 Aug 8"