A MAP Kinase Targeted by Endotoxin and Hyperosmolarity in Mammalian Cells

TLDR

Mammalian cells respond to endotoxic lipopolysaccharide by activating protein‑kinase cascades that induce gene expression, and the p38 MAP kinase shares distinctive phosphorylation‑site sequences with yeast HOG1, distinguishing it from other MAP kinases. The study cloned the tyrosine‑phosphorylated p38 kinase and showed that both p38 and yeast HOG1 become tyrosine‑phosphorylated in response to osmotic changes. The results link mammalian p38 signaling with yeast HOG1, demonstrating a conserved stress‑responsive pathway.

Abstract

Mammalian cells respond to endotoxic lipopolysaccharide (LPS) by activation of protein kinase cascades that lead to new gene expression. A protein kinase, p38, that was tyrosine phosphorylated in response to LPS, was cloned. The p38 enzyme and the product of the Saccharomyces cerevisiae HOG1 gene, which are both members of the mitogen-activated protein (MAP) kinase family, have sequences at and adjacent to critical phosphorylation sites that distinguish these proteins from most other MAP kinase family members. Both HOG1 and p38 are tyrosine phosphorylated after extracellular changes in osmolarity. These findings link a signaling pathway in mammalian cells with a pathway in yeast that is responsive to physiological stress.