High-osmolarity glycerol (HOG) pathway (WP2838)

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.

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