Hog1p is a mitogen-activated protein kinase (MAPK) integral to the osmoregulatory signal transduction cascade (HOG signaling pathway) which affects gene expression, G1 and G2 cell cycle progression, and cellular ion levels in response to hyperosmotic stress (1 and a comprehensive review of the HOG pathway can be found in 9). Loss of Hog1p activity results in reduced growth on high osmolarity media, abnormal cell and budding morphology, and osmolarity-induced activation of the pheromone response pathway (1, 10). Constitutive activation of Hog1p has been shown to be lethal (11). HOG1 is the yeast homolog of the mammalian MAPK p38, which is involved in the inflammatory and stress responses (12, 13).

Shortly after S. cerevisiae cells are exposed to hyperosmotic stress, Hog1p is phosphorylated on Thr174 and Tyr176 by the MAPKK Pbs2p (1). Activation of Hog1p leads to its Nmd5p-dependent nuclear import (14). After the cell has equilibrated to the hyperosmotic environment, Hog1p is dephosphorylated by the phosphatases Ptc1p, Ptc2p, Ptc3p, Ptp2p, and Ptp3p (15, 16, 3) and then exported from the nucleus by the karyopherin, Crm1p (14).

Nuclear-localized Hog1p mediates the upregulation of nearly 600 genes by phosphorylating osmoresponsive transcription factors, such as Msn2p/Msn4p, Sko1p, Hot1p, and Smp1p (reviewed in 9 and 17). Phosphorylation of target proteins can lead to the recruitment of other transcription factors that enlist the transcription machinery, but Hog1p has been shown to directly recruit Pol II as well (5, 18). Interaction between Hog1p and the histone deactylase Rpd3p targets the Rpd3p/Sin3p/Sap30p complex to the promoters of osmotic stress genes, resulting in chromatin modification and transcription initiation (19). Additional non-transcription factor targets of Hog1p include the Na+/H+ antiporter Nha1p; the potassium channel Tok1p; the cell cycle regulators Sic1p and Hsl1p; the osmosensor Sho1p; and the protein kinase regulator Ste50p (20, 21, 22, 23, 24).

Last updated: 2010-01-04