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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    • "Another mechanism is cross-inhibition by one MAPK pathway of other MAPK pathways. Although the Hog1 MAPK module (Ste11/Pbs2/Hog1) shares many upstream components with the FIG Kss1 MAPK module (Ste11/Ste7/ Kss1), osmostress activates the Kss1 MAPK of the FIG pathway only very weakly and transiently (Shock et al. 2009; Wang et al. 2009), and glycosylation defects that activate Kss1 do not activate Hog1 (Cullen et al. 2000; Yang et al. 2009). In the absence of Pbs2 or Hog1, however, osmostress activates Kss1 robustly and Fus3 to a lesser degree, induces Kss1/Fus3-dependent genes, and induces FIG/mating-like polarized cell growth (O'Rourke and Herskowitz 1998, 2004; Pitoniak et al. 2009). "
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    • "This connection was uncovered by characterizing the newly identified plasma-membrane regulator Opy2 (Wu et al. 2006; Ekiel et al. 2009; Yang et al. 2009; Yamamoto et al. 2010; Cappell and Dohlman 2011), which regulates the Ste11 branch of the high-osmolarity glycerol response (HOG) MAPK pathway (Hohmann et al. 2007; Saito 2010). Opy2 is also thought to regulate the filamentous growth pathway (Yang et al. 2009; Yamamoto et al. 2010). We confirmed that Opy2 is a major regulator of the filamentous growth pathway, and we identified Mig1 and Mig2 as Opy2-interacting proteins that coregulate the filamentous growth pathway. "
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