| Title: | Osmostress enhances activating phosphorylation of Hog1 MAP kinase by mono-phosphorylated Pbs2 MAP2K |
| Author(s): | Tatebayashi K; Yamamoto K; Tomida T; Nishimura A; Takayama T; Oyama M; Kozuka-Hata H; Adachi-Akahane S; Tokunaga Y; Saito H; |
| Address: | "Laboratory of Molecular Genetics, Frontier Research Unit, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. Division of Molecular Cell Signaling, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan. Department of Physiology, School of Medicine, Faculty of Medicine, Toho University, Tokyo, Japan. Medical Proteomics Laboratory, Institute of Medical Science, The University of Tokyo, Tokyo, Japan. Molecular Profiling Research Center for Drug Discovery, National Institute of Advanced Industrial Science and Technology, Tokyo, Japan" |
| ISSN/ISBN: | 1460-2075 (Electronic) 0261-4189 (Print) 0261-4189 (Linking) |
| Abstract: | "The MAP kinase (MAPK) Hog1 is the central regulator of osmoadaptation in yeast. When cells are exposed to high osmolarity, the functionally redundant Sho1 and Sln1 osmosensors, respectively, activate the Ste11-Pbs2-Hog1 MAPK cascade and the Ssk2/Ssk22-Pbs2-Hog1 MAPK cascade. In a canonical MAPK cascade, a MAPK kinase kinase (MAP3K) activates a MAPK kinase (MAP2K) by phosphorylating two conserved Ser/Thr residues in the activation loop. Here, we report that the MAP3K Ste11 phosphorylates only one activating phosphorylation site (Thr-518) in Pbs2, whereas the MAP3Ks Ssk2/Ssk22 can phosphorylate both Ser-514 and Thr-518 under optimal osmostress conditions. Mono-phosphorylated Pbs2 cannot phosphorylate Hog1 unless the reaction between Pbs2 and Hog1 is enhanced by osmostress. The lack of the osmotic enhancement of the Pbs2-Hog1 reaction suppresses Hog1 activation by basal MAP3K activities and prevents pheromone-to-Hog1 crosstalk in the absence of osmostress. We also report that the rapid-and-transient Hog1 activation kinetics at mildly high osmolarities and the slow and prolonged activation kinetics at severely high osmolarities are both caused by a common feedback mechanism" |
| Keywords: | HEK293 Cells Humans Intracellular Signaling Peptides and Proteins MAP Kinase Kinase Kinases MAP Kinase Signaling System/*genetics Membrane Proteins Mitogen-Activated Protein Kinase Kinases/genetics/metabolism Mitogen-Activated Protein Kinases/genetics/*me; |
| Notes: | "MedlineTatebayashi, Kazuo Yamamoto, Katsuyoshi Tomida, Taichiro Nishimura, Akiko Takayama, Tomomi Oyama, Masaaki Kozuka-Hata, Hiroko Adachi-Akahane, Satomi Tokunaga, Yuji Saito, Haruo eng 24247034/MEXT | Japan Society for the Promotion of Science (JSPS)/International 16H04761/MEXT | Japan Society for the Promotion of Science (JSPS)/International 17K15083/MEXT | Japan Society for the Promotion of Science (JSPS)/International 17H06017/MEXT | Japan Society for the Promotion of Science (JSPS)/International 19K06548/MEXT | Japan Society for the Promotion of Science (JSPS)/International 25440042/MEXT | Japan Society for the Promotion of Science (JSPS)/International 16H06578/MEXT | Japan Society for the Promotion of Science (JSPS)/International 150075/Sumitomo Foundation/International 1732/Salt Science Research Foundation/International Japan Foundation for Applied Enzymology/International Mochida Memorial Foundation for Medical and Pharmaceutical Research/International GPLLI program from MEXT/International Research Support, Non-U.S. Gov't England 2020/02/06 EMBO J. 2020 Mar 2; 39(5):e103444. doi: 10.15252/embj.2019103444. Epub 2020 Feb 3" |
