| Title: | Modularity of MAP kinases allows deformation of their signalling pathways |
| Author(s): | Mody A; Weiner J; Ramanathan S; |
| ISSN/ISBN: | 1476-4679 (Electronic) 1465-7392 (Print) 1465-7392 (Linking) |
| Abstract: | "Eukaryotic protein kinase pathways have both grown in number and changed their network architecture during evolution. We wondered if there are pivotal proteins in these pathways that have been repeatedly responsible for forming new connections through evolution, thus changing the topology of the network; and if so, whether the underlying properties of these proteins could be exploited to re-engineer and rewire these pathways. We addressed these questions in the context of the mitogen-activated protein kinase (MAPK) pathways. MAPK proteins were found to have repeatedly acquired new specificities and interaction partners during evolution, suggesting that these proteins are pivotal in the kinase network. Using the MAPKs Fus3 and Hog1 of the Saccharomyces cerevisiae mating and hyper-osmolar pathways, respectively, we show that these pivotal proteins can be re-designed to achieve a wide variety of changes in the input-output properties of the MAPK network. Through an analysis of our experimental results and of the sequence and structure of these proteins, we show that rewiring of the network is possible due to the underlying modular design of the MAPKs. We discuss the implications of our findings on the radiation of MAPKs through evolution and on how these proteins achieve their specificity" |
| Keywords: | "Conserved Sequence Enzyme Activation Evolution, Molecular Glycerol/metabolism *MAP Kinase Signaling System Mitogen-Activated Protein Kinases/chemistry/*metabolism Models, Molecular Osmolar Concentration Pheromones/metabolism Protein Binding Protein Struct;" |
| Notes: | "MedlineMody, Areez Weiner, Joan Ramanathan, Sharad eng 2P50GM068763/GM/NIGMS NIH HHS/ P50 GM068763-03/GM/NIGMS NIH HHS/ P50 GM068763-08/GM/NIGMS NIH HHS/ P50 GM068763-06/GM/NIGMS NIH HHS/ P50 GM068763-07/GM/NIGMS NIH HHS/ P50 GM068763-01/GM/NIGMS NIH HHS/ P50 GM068763-05/GM/NIGMS NIH HHS/ P50 GM068763-02/GM/NIGMS NIH HHS/ P50 GM068763-03S1/GM/NIGMS NIH HHS/ P50 GM068763-04/GM/NIGMS NIH HHS/ P50 GM068763-09/GM/NIGMS NIH HHS/ P50 GM068763/GM/NIGMS NIH HHS/ Letter Research Support, N.I.H., Extramural England 2009/03/20 Nat Cell Biol. 2009 Apr; 11(4):484-91. doi: 10.1038/ncb1856. Epub 2009 Mar 22" |
