Abstract
The yeast Hog1 protein is both functionally and structurally similar to the mammalian p38, belonging to the same family of mitogen-activated protein (MAP) kinases and responding to extracellular changes in osmolarity. Since p38 mediates lipopolysaccharide (LPS) effects in mammalian cells, we now tested the responsiveness of Hog1 upon exposure of the yeast Saccharomyces cerevisiae to bacterial LPS. In the presence of Escherichia coli LPS (100 ng/ml) and an endotoxically active, hexaacylated, synthetic lipid A (compound 506; 100 ng/ml), Hog1 becomes phosphorylated with a maximum of phosphorylation between 3 and 6 h, whereas a tetraacylated, inactive form of lipid A (compound 406) did not cause any modification in the phosphorylation state of Hog1. A triple labeling immunocytochemical study showed that phosphorylated Hog1 translocates into the nucleus after a 90-min incubation and becomes sparsely located in the cytoplasm. The translocation of the phospho-Hog1 is preceded by an increased expression of the HOG1 gene and concomitant with the expression of the Hog1 target gene, GPD1. We also observed that cells unable to synthesize Hog1 do not resist LPS as efficiently as wild-type cells. 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.
Highlights
Kinase, which responds to increased extracellular osmolarity and is essential for cell survival under these conditions (Ref. 2, and for review, see Refs. 3 and 4)
Previous studies focusing in the response to extracellular changes in osmolarity showed a physiological analogy between mammalian p38 stress kinase and the yeast Hog1 protein, as expected from their extensive sequence homology [22]
The present study extends the physiological homology between yeast Hog1 and mammalian p38 protein to the context of the response to bacterial endotoxin, a prototypical trigger of inflammatory responses in mammalian systems [29]
Summary
Kinase, which responds to increased extracellular osmolarity and is essential for cell survival under these conditions (Ref. 2, and for review, see Refs. 3 and 4). The difference between the two forms of lipid A described by us excludes the hypothesis that the effect observed upon exposure to LPS or lipid A could be due to a disturbance of the cell membrane by hydrophobic substances since the biologically inactive synthetic lipid A compound 406 does not induce Hog1 phosphorylation.
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