Disease relevance of SLN1

• The C-terminal response regulator domains of SLN1 and SSK1 and full-length YPD1 have been overexpressed and purified from E. coli [1].

High impact information on SLN1

• Ypd1p binds to both Sln1p and Ssk1p and mediates the multistep phosphotransfer reaction (phosphorelay) [2].
• The transmembrane protein Sln1p contains an extracellular sensor domain and cytoplasmic histidine kinase and receiver domains, whereas the cytoplasmic protein Ssk1p contains a receiver domain [2].
• Pbs2p was activated by MAP kinase kinase kinases (MAPKKKs) Ssk2p and Ssk22p that are under the control of the SLN1-SSK1 two-component osmosensor [3].
• The finding of SLN1 demonstrates that a mode of signal transduction similar to the bacterial two-component design operates in eukaryotes as well [4].
• A missense mutation in SLN1 is lethal in the absence but not in the presence of the N-end rule pathway, a ubiquitin-dependent proteolytic system [4].

Biological context of SLN1

• SLN1 also activates an MCM1-dependent reporter gene, P-lacZ, but this function is independent of Ssk1p [5].
• Carbon source regulation of PIS1 gene expression in Saccharomyces cerevisiae involves the MCM1 gene and the two-component regulatory gene, SLN1 [6].
• Activated alleles of SLN1 (sln1*) were previously identified that appear to increase the level of phosphorylation of downstream targets Ssk1p and Skn7p [7].
• In principle, the phenotype of sln1* alleles could arise from an increase in autophosphorylation or phosphotransfer activities or a decrease in an intrinsic or extrinsic dephosphorylation activity [7].
• The multifunctional Skn7 protein is important in oxidative as well as osmotic stress; however, the Skn7p receiver domain aspartate that is the phosphoacceptor in the SLN1 pathway is dispensable for oxidative stress [8].

Anatomical context of SLN1

• Reductions in turgor caused by either hyperosmotic stress, nystatin, or removal of cell wall activate MAPK Hog1 specifically through the SLN1 branch, but not through the SHO1 branch of the high osmolarity glycerol pathway [9].
• Dimethyl sulfoxide (DMSO) treatment, which rigidifies the cell membrane, also activates the HOG pathway in both SLN1 branch- and SHO1 branch-dependent manners [10].

Associations of SLN1 with chemical compounds

• The glycerol-mediated repression of PIS1 gene expression required both the MCM1 gene and the MCEs, whereas the SLN1 gene was required for full galactose-mediated induction of a PIS1-lacZ reporter gene [6].
• The Sln1p aspartyl phosphate is then transferred to Ypd1p, which in turn transfers the phosphoryl group to a conserved aspartate on one of two response regulators, Ssk1p and Skn7p [7].
• Sln1p consists of a sensor kinase module that undergoes histidine autophosphorylation and a receiver module that autocatalytically transfers the phosphoryl group from histidine to aspartate [7].
• It is known that mutations within the histidine kinase NIK1/OS-1 gene confer resistance to iprodione and fludioxonil in Neurospora crassa, while the fungicide-insensitive S. cerevisiae has only one histidine kinase SLN1 gene in its genome [11].
• In vitro kinase assays were performed by using the Sln1 histidine kinase purified from bacteria as a fusion protein to glutathione S-transferase [12].
• The hypothesis that Sln1p kinase activity is responsive to turgor was first suggested by the increased Sln1p kinase activity in mutants lacking Fps1p in which glycerol accumulation leads to water uptake [13].

Enzymatic interactions of SLN1

• 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 [14].

Regulatory relationships of SLN1

• Modulation of Sln1 kinase activity in response to changes in the osmotic environment regulates the activity of the osmotic response mitogen-activated protein kinase pathway and the activity of the Skn7p transcription factor, both important for adaptation to changing osmotic stress conditions [15].
• Phosphorylation of Sln1p inhibits the HOG1 MAP kinase osmosensing pathway via a phosphorelay mechanism including Ypd1p and the response regulator, Ssk1p [5].

Other interactions of SLN1

• This phosphate is then sequentially transferred to Sln1p-Asp-1144, then to Ypd1p-His64, and finally to Ssk1p-Asp554 [2].
• In contrast, we show that Sln1p activation of Skn7p requires phosphorylation of D427 [5].
• This is the first example in yeast of a complete circuit linking a stimulus (carbon source) to gene regulation (PIS1) using a two-component regulator (SLN1) [6].
• Two Saccharomyces cerevisiae plasma membrane-spanning proteins, Sho1 and Sln1, function during increased osmolarity to activate a mitogen-activated protein (MAP) kinase cascade [16].
• Moreover, Hog1p activation occurred specifically through the Sln1 branch [17].

Analytical, diagnostic and therapeutic context of SLN1

• In Saccharomyces cerevisiae, a phosphorelay signal transduction pathway composed of Sln1p, Ypd1p, and Ssk1p, which are homologous to bacterial two-component signal transducers, is involved in the osmosensing mechanism [18].

References