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

Abstract

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.

The Filamentous Growth MAPK Pathway Responds to Glucose Starvation Through the Mig1/2 Transcriptional Repressors in Saccharomyces cerevisiae

“…The Opy2 G207D and Opy2 C30Y proteins were also defective for HOG pathway signaling, based on the saltdependent phosphorylation of the MAPK that functions in the HOG pathway, Hog1 ( Figure S2C). Together, our results support and extend the conclusion put forward in Yang et al (2009) that Opy2 is a general adaptor for the HOG and filamentous growth pathways that functions by plasmamembrane recruitment of Ste50.…”

“…Opy2 functions in the HOG pathway (Wu et al 2006;Ekiel et al 2009;Yang et al 2009;Yamamoto et al 2010;Cappell and Dohlman 2011) and may also regulate the filamentous growth pathway (Yang et al 2009;Yamamoto et al 2010), although this possibility has not been extensively explored (Wu et al 2006;Chen and Thorner 2007). To determine whether Opy2 regulates the filamentous growth pathway, the OPY2 gene was deleted in strains of the filamentous ( P 1278b) background (Liu et al 1996).…”

“…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).…”

TheO-Mannosyltransferase PMT4 Is Essential for Normal Appressorium Formation and Penetration inUstilago maydis

“…Given that the deletion of pmt4 does not affect cell cycle progression, mating, or polar growth, it seems unlikely that these proteins are responsible for the phenotypes we observe in U. maydis, although we are currently working to test this experimentally. Sc Fus1p, Sc Opy2p, and Sc Msb2p, components of the yeast filamentous growth mitogen-activated protein kinase pathway, have recently been described as additional PMT4 targets (Yang et al, 2009). We found that U. maydis contains only some elements of the yeast filamentous growth mitogen-activated protein kinase pathway.…”

Architecture and Biosynthesis of the Saccharomyces cerevisiae Cell Wall

“…Pmt4--initiated O--mannosylation is also necessary for cell surface delivery of Fus1, because the unglycosylated protein accumulates in the late Golgi ). Defects in Pmt4--dependent O--glycosylation of Msb2 (as well as N--glycosyation) of osmosensor Msb2 lead to activation of the filamentous growth signaling pathway (Yang et al 2009). In this case, underglycosylation may unmask a domain that normally is exposed and makes interactions when the signaling pathway is activated legitimately.…”