Pbs2

PBS2 is a gene in the budding yeast Saccharomyces cerevisiae that encodes a mitogen-activated protein kinase kinase (MAPKK). Pbs2 is a central component of the High Osmolarity Glycerol (HOG) pathway, which enables cells to adapt to high osmolarity environments.

The MAPKK phosphorylates Hog1, a downstream MAP kinase, on its activation loop, thereby activating Hog1 and promoting its translocation to the nucleus where it regulates transcription.

Upstream, Pbs2 is activated by two sensor-kinase branches: the Sln1-Ssk2/Ssk22 branch and the Sho1-Ste11 branch. Upon osmotic stress, these MAPKKKs phosphorylate Pbs2, which then activates Hog1.

Activated Hog1 controls gene expression and metabolism to restore osmotic balance, including transcription of glycerol biosynthesis genes (GPD1, GPP2) and enzymes that increase intracellular glycerol. Hog1 also coordinates cell-cycle and broader stress response programs.

Negative regulation occurs via the protein tyrosine phosphatases Ptp2 and Ptp3 that dephosphorylate Hog1.

Genetic studies show PBS2 is essential for proper osmostress response; pbs2 mutants exhibit sensitivity to high salt and fail to activate Hog1.

PBS2 belongs to a conserved family of MAPKKs; related kinases exist in other yeasts, and the Hog1 MAPK is homologous to mammalian p38, with analogous upstream MEK kinases.