LAUSR

Two stress-activated MAP kinase (SAPK) pathways in Saccharomyces cerevisiae respond to osmotic imbalances. The High Osmolarity Glycerol (HOG) pathway is activated in response to hyper-osmotic stress, whereas the Cell Wall Integrity (CWI) pathway is activated in response to hypo-osmotic stress. However, there is also evidence of complex interplay and crosstalk between the two pathways. For example, treatment with zymolyase, a mixture of cell wall degrading enzymes, is known to activate the SAPK Hog1 of the HOG pathway and the SAPK Mpk1 of the CWI pathway sequentially, with Mpk1 activation dependent upon Hog1. Additionally, the PTP2- and PTP3-encoded tyrosine-specific protein phosphatases play a key role in down-regulation of Hog1, but may also down-regulate Mpk1. In this study, we show that hyperactivation of Mpk1 in a ptp2 ptp3 null mutant is an indirect consequence of Hog1 hyperactivation, which induces accumulation of intracellular glycerol and an attendant hypo-osmotic stress. Mpk1 hyperactivity in the absence of PTP2 and PTP3 was suppressed by a hog1 null mutation, or by restoration of osmotic balance with a constitutive form of the glycerol channel Fps1. We found similarly that activation of Mpk1 in response to zymolyase treatment is partly a consequence of Hog1-driven glycerol accumulation. Thus, we have identified two conditions in which glycerol serves as a mediator of crosstalk between the HOG and CWI pathways.