Glycosylation defects activate filamentous growth Kss1 MAPK and inhibit osmoregulatory Hog1 MAPK.
The yeast filamentous growth (FG) MAP kinase (MAPK) pathway is activated under poor nutritional conditions. We found that the FG-specific Kss1 MAPK is activated by a combination of an O-glycosylation defect caused by disruption of the gene encoding the protein O-mannosyltransferase Pmt4, and an N-glycosylation defect induced by tunicamycin. The O-glycosylated membrane proteins Msb2 and Opy2 are both essential for activating the FG MAPK pathway, but only defective glycosylation of Msb2 activates the FG MAPK pathway. Although the osmoregulatory HOG (high osmolarity glycerol) MAPK pathway and the FG MAPK pathway share almost the entire upstream signalling machinery, osmostress activates only the HOG-specific Hog1 MAPK. Conversely, we now show that glycosylation defects activate only Kss1, while activated Kss1 and the Ptp2 tyrosine phosphatase inhibit Hog1. In the absence of Kss1 or Ptp2, however, glycosylation defects activate Hog1. When Hog1 is activated by glycosylation defects in ptp2 mutant, Kss1 activation is suppressed by Hog1. Thus, the reciprocal inhibitory loop between Kss1 and Hog1 allows only one or the other of these MAPKs to be stably activated under various stress conditions.
Division of Molecular Cell Signaling, Institute of Medical Sciences, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo, Japan.
Hui-Yu
HY
Yang
Kazuo
K
Tatebayashi
Katsuyoshi
K
Yamamoto
Haruo
H
Saito
D004791:Enzyme Inhibitors / Q000494:pharmacology; D015966:Gene Expression Regulation, Fungal; D006031:Glycosylation; D008364:Mannosyltransferases / Q000172:deficiency; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008954:Models, Biological; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D012440:Saccharomyces / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D014415:Tunicamycin / Q000494:pharmacology
D004791:Enzyme Inhibitors; D029701:Saccharomyces cerevisiae Proteins; D014415:Tunicamycin; D008364:Mannosyltransferases; C082696:protein O-mannosyltransferase; C075580:FUS3 protein, S cerevisiae; C088589:HOG1 protein, S cerevisiae; C541984:KSS1 protein, S cerevisiae; D020928:Mitogen-Activated Protein Kinases; D017027:Protein Tyrosine Phosphatases; C528257:Ptp2 protein, S cerevisiae