| Title: | "Bistability, stochasticity, and oscillations in the mitogen-activated protein kinase cascade" |
| Author(s): | Wang X; Hao N; Dohlman HG; Elston TC; |
| Address: | "Department of Statistics and Operations Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7365, USA" |
| DOI: | 10.1529/biophysj.105.073874 |
| ISSN/ISBN: | 0006-3495 (Print) 1542-0086 (Electronic) 0006-3495 (Linking) |
| Abstract: | "Signaling pathways respond to stimuli in a variety of ways, depending on the magnitude of the input and the physiological status of the cell. For instance, yeast can respond to pheromone stimulation in either a binary or graded fashion. Here we present single cell transcription data indicating that a transient binary response in which all cells eventually become activated is typical. Stochastic modeling of the biochemical steps that regulate activation of the mitogen-activated protein kinase Fus3 reveals that this portion of the pathway can account for the graded-to-binary conversion. To test the validity of the model, genetic approaches are used to alter expression levels of Msg5 and Ste7, two of the proteins that negatively and positively regulate Fus3, respectively. Single cell measurements of the genetically altered cells are shown to be consistent with predictions of the model. Finally, computational modeling is used to investigate the effects of protein turnover on the response of the pathway. We demonstrate that the inclusion of protein turnover can lead to sustained oscillations of protein concentrations in the absence of feedback regulation. Thus, protein turnover can profoundly influence the output of a signaling pathway" |
| Keywords: | "Biological Clocks/drug effects/*physiology Computer Simulation Gene Expression Regulation/drug effects/*physiology MAP Kinase Signaling System/drug effects/*physiology *Models, Biological Models, Statistical Pheromones/*pharmacology Saccharomyces cerevisi;" |
| Notes: | "MedlineWang, Xiao Hao, Nan Dohlman, Henrik G Elston, Timothy C eng R01 GM059167/GM/NIGMS NIH HHS/ R01 GM073180/GM/NIGMS NIH HHS/ GM059167/GM/NIGMS NIH HHS/ GM073180/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. 2005/12/20 Biophys J. 2006 Mar 15; 90(6):1961-78. doi: 10.1529/biophysj.105.073874. Epub 2005 Dec 16" |
