Disease relevance of HOG1

• The possible function of Hog1 activation during heat stress was examined, and it was found that the hog1 delta strain does not recover as rapidly from heat stress as well as the wild type [1].
• Osmolarity hypersensitivity of hog1 deleted mutants is suppressed by mutation in KSS1 in budding yeast Saccharomyces cerevisiae [2].
• Given the conserved nature of Gcn2p and Hog1p pathways, this mechanism of FK506 toxicity could be relevant to the non-therapeutic effects of FK506 therapy [3].
• Serotype A hog1delta and pbs2delta mutants are attenuated in virulence, further underscoring the role of the Pbs2-Hog1 MAPK cascade in the pathogenesis of cryptococcosis [4].
• We conclude that the yeast S. cerevisiae is able to respond to the presence of Gram-negative bacteria endotoxin and that Hog1 is involved in this response [5].

High impact information on HOG1

• Hog1 phosphorylation stimulates Nha1 activity, and this is crucial for the rapid reassociation of proteins with their target sites in chromatin [6].
• This initial response to hyperosmolarity precedes and temporally regulates the activation of stress-response genes that depends on Hog1 phosphorylation of transcription factors in the nucleus [6].
• A rapid, PBS2-dependent tyrosine phosphorylation of HOG1 protein occurred in response to increases in extracellular osmolarity [7].
• While it is has been shown that the lipid kinase Fab1p and its product phosphatidylinositol 3,5-bisphosphate, and not the mitogen-activated protein kinase Hog1p, are central to this regulatory pathway, key effectors still await identification [8].
• In yeast, a transcription repressor, Sko1, mediates regulation of the sodium-pump ENA1 gene by the Hog1 MAP kinase [9].

Chemical compound and disease context of HOG1

• It was also found that protein tyrosine phosphatases (PTPs) Ptp2 and Ptp3, which inactivate Hog1, have two functions during heat stress [1].

Biological context of HOG1

• Phosphorylation of Sln1p inhibits the HOG1 MAP kinase osmosensing pathway via a phosphorelay mechanism including Ypd1p and the response regulator, Ssk1p [10].
• The HOG signal pathway of the yeast Saccharomyces cerevisiae is defined by the PBS2 and HOG1 genes encoding members of the MAP kinase kinase and of the MAP kinase family, respectively [11].
• Mutations in this pathway (deletions of PBS2 or HOG1, or point mutations in HOG1) almost completely abolish the induction of transcription by osmotic stress that is mediated by stress response elements (STREs) [11].
• HOG1 was also required for citric acid-induced up-regulation of Ssa1p and Eno2p [12].
• Although Hog1 nuclear export correlates with its dephosphorylation, we find that dephosphorylation is not necessary for export [13].

Anatomical context of HOG1

• Here, using the tailored microarray, the role of the HOG1 pathway in the regulation of the transcriptional compensatory response to cell wall damage was evaluated by comparing the transcriptional profiles of a hog1 mutant and a wild-type strain in the presence of Congo red [14].
• In eukaryotic cells, environmental stress signals are transmitted by evolutionarily conserved MAPKs, such as Hog1 in the budding yeast Saccharomyces cerevisiae, Spc1 in the fission yeast Schizosaccharomyces pombe and p38/JNK in mammalian cells [15].

Associations of HOG1 with chemical compounds

• HOG1 negatively regulated the expression of a number of proteins in response to citric acid stress, including Bmh1p [12].
• ALD2 exhibits maximum induction with 0.3 M NaCl, negative regulation by protein kinase A and dependence on PBS2 and HOG1 protein kinases for osmotic induction [16].
• Two protein tyrosine phosphatases, Ptp2 and Ptp3, modulate the subcellular localization of the Hog1 MAP kinase in yeast [13].
• A catalytically inactive Cys-to-Ser Ptp2p mutant (Ptp2(C/S)p) is tightly bound to tyrosine-phosphorylated Hog1p in vivo [17].
• Hog1p is activated by Pbs2p through phosphorylation of specific threonine and tyrosine residues [17].

Physical interactions of HOG1

• SGD1 interacts genetically with both PLC1 and HOG1 (which encodes an osmosensing mitogen-activated protein kinase) [18].
• Fus1p interacts with components of the Hog1p mitogen-activated protein kinase and Cdc42p morphogenesis signaling pathways to control cell fusion during yeast mating [19].
• Both two-hybrid analyses and coprecipitation assays demonstrated that Hog1 binds strongly to the C-terminal region of Rck2 [20].
• Hog1 interacts physically with Rpd3 in vivo and in vitro and, on stress, targets the deacetylase to specific osmostress-responsive genes [21].

Enzymatic interactions of HOG1

• Disruption of PTP2 leads to elevated levels of tyrosine-phosphorylated Hog1p following exposure of cells to high osmolarity [17].
• The relationship between the two Sln1p branches is unclear, however, the requirement for unphosphorylated pathway intermediates in Hog1p pathway activation and for phosphorylated intermediates in the activation of the Mcm1p reporter suggests that the two Sln1p branches are reciprocally regulated [22].
• We show that Hog1 is robustly phosphorylated in a Pbs2-dependent way during oxidative stress, and that Rck2 also is phosphorylated under these circumstances [23].
• Hog1 phosphorylated Smp1 in vitro at the C-terminal region [24].
• Hog1 phosphorylates Sko1 in vitro at multiple sites within the N-terminal region [25].

Regulatory relationships of HOG1

• We suggest that Hog1p may prevent osmolarity-induced cross talk by inhibiting Sho1p, perhaps as part of a feedback control on the HOG pathway [26].
• Northern blot analyses suggest that Hog1p regulates Ptp2p and/or Ptp3p activity at the posttranscriptional level [17].
• Thus, one function of Ptc1 is to inactivate Hog1 [27].
• Overexpression of the protein tyrosine phosphatase Ptp2p suppresses the lethality of these mutations by dephosphorylating Hog1p [17].
• Overexpression of SMP1 induced Hog1-dependent expression of osmoresponsive genes such as STL1, whereas smp1Delta cells were defective in their expression [24].

Other interactions of HOG1

• We found that mutations in the HOG1 gene, encoding the p38-type MAPK of the HOG pathway, and in the PBS2 gene, encoding the activating kinase for Hog1p, allowed osmolarity-induced activation of the pheromone response pathway [26].
• Finally, we have found that pseudohyphal growth exhibited by wild-type (HOG1) strains depends on SHO1, suggesting that Sho1p may be a receptor that feeds into the pseudohyphal growth pathway [26].
• Consistent with its role as a negative regulator of Hog1, which accumulates in the nucleus upon activation, Ptc1 was found in both the nucleus and the cytoplasm [27].
• The second mechanism of HOG1 MAP kinase activation is independent of the two-component osmosensor and involves the SHO1 transmembrane protein and the STE11 MAPKKK [28].
• Moreover, Hog1p activation occurred specifically through the Sln1 branch [29].
• Hog1p is shown to affect Fps1p phosphorylation [30].

Analytical, diagnostic and therapeutic context of HOG1

• DNA microarrays were used to characterize the global transcriptional responses of HOG1 and hog1 cells to three stress conditions that activate the Hog1 SAPK: osmotic stress, oxidative stress, and heavy metal stress [31].
• Sequence analysis of a 37.6 kbp cosmid clone from the right arm of Saccharomyces cerevisiae chromosome XII, carrying YAP3, HOG1, SNR6, tRNA-Arg3 and 23 new open reading frames, among which several homologies to proteins involved in cell division control and to mammalian growth factors and other animal proteins are found [32].
• Genetic and microarray analysis indicates that high osmolarity extends the life span by activating Hog1p, leading to an increase in the biosynthesis of glycerol from glycolytic intermediates [33].
• Western blot analysis of Wt and the tcsBtriangle up strains indicated that when stressed with H(2)O(2), phosphorylation of Hog1p still occurs in the mutant [34].
• To identify the genes regulated downstream of OS-2 MAP kinase, quantitative real-time RT-PCR analysis was conducted in selected genes based on Hog1 MAP kinase regulated genes in yeast [35].

References