Dissecting yeast Hog1 MAP kinase pathway using a chemical genetic approach.
Using a chemical genetic approach, we identified four novel physiological substrates of Hog1 kinase (Krs1, Tdh3, Hsp26, and Shm2). These substrates suggest plausible mechanisms for actin reorganization, cell cycle arrest and regulation of protein synthesis observed upon osmotic stress. We further show that the human homolog of Shm2 (SHMT1) is a novel physiological substrate of p38 MAP kinase in vitro and in vivo. Down-regulation of its enzymatic activity was observed following p38-mediated phosphorylation revealing a potential cancer-modulating property of p38 MAP kinase. This screen has uncovered several novel Hog1 substrates that provide new avenues for investigation into the mechanism of osmoadaptation by this kinase.
Kim
Sungjoon
S
Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907, USA.
Shah
Kavita
K
D015536:Down-Regulation; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); D006360:Heat-Shock Proteins; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009997:Osmotic Pressure; D010766:Phosphorylation; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D013379:Substrate Specificity; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D005656:Fungal Proteins; C499528:HSP26 protein, S cerevisiae; D006360:Heat-Shock Proteins; D029701:Saccharomyces cerevisiae Proteins; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); C465226:TDH3 protein, S cerevisiae; C088589:HOG1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases