High-osmolarity glycerol (HOG) pathway (WP2838)

Saccharomyces cerevisiae

The high-osmolarity glycerol (HOG) pathway is a mitogen-activated protein kinase (MAPK) pathway that regulates stress response in Saccharomyces cerevisiae mainly as it relates to the adaptation of yeast cells to hyperosmotic stress. Two input branches activate the MAPK module by different mechanisms. The Sho1 branch requires Sho1p and the mucin-like proteins Hkr1p and Msb2p to sense osmostress. Sho1p-dependent signalling also requires small G-protein Cdc42p, and PAK family members Ste20 and Cla4. The target of Ste20p is the MAPKKK Ste11p, which activates the MAPKK Pbs2p under hyperosmotic conditions, resulting in Hog1p activation. Another branch, leading to the activation of Pbs2, involves a ‘two-component’ phospho-relay signalling system that involves transmembrane protein Sln1p and response regulator proteins Ypd1p and Ssk1p. In this branch, the two redundant MAPKKKs Ssk2p and Ssk22p participate in the phosphorylation of Pbs2p, which is responsible for the final activation of Hog1p. Once Hog1p is activated, it coordinates several processes necessary for cellular adaptation to osmotic stress, including ubiquitination, chromatin remodelling, the transcriptional program, mRNA export, translational response, and cell cycle progression. In addition to its main role in the regulation of hyperosmotic stress responses, the HOG pathway is also activated in response to oxidatiion, acids stress, organic compounds, metals, and freeze or heat stress.


Stacia , Kristina Hanspers , Elisa Cirillo , Egon Willighagen , and Eric Weitz


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Saccharomyces cerevisiae



Pathway Ontology

stress response pathway signaling pathway mitogen activated protein kinase signaling pathway regulatory pathway


Label Type Compact URI Comment
PP2C3 Protein uniprot:P34221
SSK22 Protein uniprot:P25390
SSK1 Protein uniprot:Q07084
YPD1 Protein uniprot:Q07688
CLA4 Protein uniprot:P48562
HOG1 Protein uniprot:P32485
SLN1 Protein uniprot:P39928
SKO1 Protein uniprot:Q02100
MSN4 Protein uniprot:P33749
PTC1 Protein uniprot:P35182
PTP2 Protein uniprot:P29461
HKR1 Protein uniprot:P41809
STE50 Protein uniprot:P25344
PBS2 Protein uniprot:P08018
HOT1 Protein uniprot:Q03213
OPY2 Protein uniprot:Q06810
STE11 Protein uniprot:P23561
SMP1 Protein uniprot:P38128
CDC42 Protein uniprot:P19073
STE20 Protein uniprot:Q03497
SSK2 Protein uniprot:P53599
MSB2 Protein uniprot:P32334
HOG1 Protein uniprot:P32485
MSN2 Protein uniprot:P33748
SHO1 Protein uniprot:P40073


  1. Control of high osmolarity signalling in the yeast Saccharomyces cerevisiae. Hohmann S. FEBS Lett. 2009 Dec 17;583(24):4025–9. PubMed Europe PMC Scholia
  2. The high-osmolarity glycerol (HOG) and cell wall integrity (CWI) signalling pathways interplay: a yeast dialogue between MAPK routes. Rodríguez-Peña JM, García R, Nombela C, Arroyo J. Yeast. 2010 Aug;27(8):495–502. PubMed Europe PMC Scholia