| Title: | Oscillatory phosphorylation of yeast Fus3 MAP kinase controls periodic gene expression and morphogenesis |
| Author(s): | Hilioti Z; Sabbagh W; Paliwal S; Bergmann A; Goncalves MD; Bardwell L; Levchenko A; |
| Address: | "Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA" |
| DOI: | 10.1016/j.cub.2008.09.027 |
| ISSN/ISBN: | 0960-9822 (Print) 0960-9822 (Linking) |
| Abstract: | "Signal-transduction networks can display complex dynamic behavior such as oscillations in the activity of key components [1-6], but it is often unclear whether such dynamic complexity is actually important for the network's regulatory functions [7, 8]. Here, we found that the mitogen-activated protein kinase (MAPK) Fus3, a key regulator of the yeast mating-pheromone response, undergoes sustained oscillations in its phosphorylation and activation state during continuous pheromone exposure. These MAPK activity oscillations led to corresponding oscillations in mating-gene expression. Oscillations in MAPK activity and gene expression required the negative regulator of G protein signaling Sst2 and partially required the MAPK phosphatase Msg5. Peaks in Fus3 activation correlated with periodic rounds of cell morphogenesis, with each peak preceding the formation of an additional mating projection. Preventing projection formation did not eliminate MAPK oscillation, but preventing MAPK oscillation blocked the formation of additional projections. A mathematical model was developed that reproduced several features of the observed oscillatory dynamics. These observations demonstrate a role for MAPK activity oscillation in driving a periodic downstream response and explain how the pheromone signaling pathway, previously thought to desensitize after 1-3 hr, controls morphology changes that continue for a much longer time" |
| Keywords: | "*Biological Clocks Enzyme Activation GTPase-Activating Proteins/metabolism *Gene Expression Regulation, Fungal Mitogen-Activated Protein Kinases/*metabolism *Morphogenesis Phosphorylation Protein Tyrosine Phosphatases/metabolism Saccharomyces cerevisiae/*;" |
| Notes: | "MedlineHilioti, Zoe Sabbagh, Walid Jr Paliwal, Saurabh Bergmann, Adriel Goncalves, Marcus D Bardwell, Lee Levchenko, Andre eng R01 GM060366-09/GM/NIGMS NIH HHS/ R33 GM069013-04/GM/NIGMS NIH HHS/ R33 GM069013/GM/NIGMS NIH HHS/ GM76516/GM/NIGMS NIH HHS/ U54 RR020839/RR/NCRR NIH HHS/ R01 GM084332/GM/NIGMS NIH HHS/ GM84332/GM/NIGMS NIH HHS/ GM60366/GM/NIGMS NIH HHS/ GM69013/GM/NIGMS NIH HHS/ R01 GM075309/GM/NIGMS NIH HHS/ P50 GM076516-020003/GM/NIGMS NIH HHS/ GM75309/GM/NIGMS NIH HHS/ R01 GM072024/GM/NIGMS NIH HHS/ GM72024/GM/NIGMS NIH HHS/ P50 GM076516/GM/NIGMS NIH HHS/ RR020839/RR/NCRR NIH HHS/ R01 GM060366/GM/NIGMS NIH HHS/ R21 GM069013/GM/NIGMS NIH HHS/ R01 GM072024-04/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S. England 2008/11/04 Curr Biol. 2008 Nov 11; 18(21):1700-6. doi: 10.1016/j.cub.2008.09.027. Epub 2008 Oct 30" |
