Regulation of MAP kinase Hog1 by calmodulin during hyperosmotic stress.

Mitogen-activated protein kinase (Hog1 in yeast and ortholog p38 in human cells) plays a critical role in the signal transduction pathway that is rapidly activated under multiple stress conditions. Environmental stress stimuli such as hyperosmotic stress cause changes in cellular ATP metabolism required for hyperosmotic stress tolerance. Furthermore, hyperosmotic stress induces rapid Ca2+ signals in eukaryotic cells. These Ca2+ signals can be decoded by Ca2+ sensor calmodulin (CaM). By using genetic and biochemical approaches, we demonstrate that Hog1 is a novel CaM-binding protein, and that CaM-binding to Hog1 is involved in the mediation of the hyperosmotic stress signaling pathway. In addition, we show that p38α, a human ortholog of Hog1, interacts with CaM, suggesting that the CaM-binding feature of Hog1/p38α is evolutionarily conserved in eukaryotic cells. Hog1 is likely involved in cellular ATP regulation through CaM signaling during hyperosmotic stress. Therefore, this work suggests that Hog1 plays an important role in connecting CaM signaling with the hyperosmotic stress pathway by directly interacting with CaM in Saccharomyces cerevisiae.