Glycosylation defects activate filamentous growth Kss1 MAPK and inhibit osmoregulatory Hog1 MAPK

Division of Molecular Cell Signaling, Institute of Medical Sciences, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo, Japan.
The EMBO Journal (Impact Factor: 10.43). 05/2009; 28(10):1380-91. DOI: 10.1038/emboj.2009.104
Source: PubMed


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.

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Available from: Kazuo Tatebayashi, Jul 03, 2015
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    • "Therefore, the N-terminal extracellular region of MoMsb2 likely plays a positive role in appressorium formation and virulence in M. oryzae, which is similar to the observations with its ortholog in U. maydis (Lanver et al., 2010). Whereas deletion of the PMT4 O-manosyltransferase gene in S. cerevisiae lead to the underglycosylation of Msb2 and activation of FG pathway (Yang et al., 2009), deletion of its ortholog caused defects in appressorium development and virulence in U. maydis (Fernández-Álvarez et al., 2009). It is likely that glycosylation by the PMT4 ortholog also is important for MoMsb2 functions in appressorium morphogenesis and plant infection in M. oryzae. "
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    • "Underglycosylated Msb2 mimics the activated form of the protein, because the extracellular domain is inhibitory and activates the MAPK pathway. In protein glycoslyation mutants, Msb2 is underglycosylated (Cullen et al. 2004; Yang et al. 2009), and the MAPK pathway is active (Cullen et al. 2000). Indeed, most perturbations to Msb2's mucin homology domain (which is heavily glycosylated in mammalian mucins) (Silverman et al. 2003) results in a hyperactive protein (Cullen et al. 2004). "
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