Mitogen-activated protein kinase cascades and the signaling of hyperosmotic stress to immediate early genes

Among prokaryotes and lower eukaryotes, the threat of exposure to hyperosmotic stress is ubiquitous. Among higher eukaryotes, in contrast, only specific tissues are routinely exposed to marked hypertonicity. The mammalian renal medulla, the prototypical example, is continually subjected to an elevated solute concentration as a consequence of the renal concentrating mechanism. Until recently, the investigative focus has concerned the effects of diverse solutes on the regulation of genes essential for the adaptive accumulation of osmotically active organic solutes. Recent and sweeping developments elucidating the molecular mechanisms underlying stress signaling to the nucleus have focused interest on earlier events in the response to hyperosmotic stress. Such events include the transcriptional activation and post-translational modification of transcriptional activating proteins, a large subset of which represent the protein products of so-called immediate early genes. This review highlights developments in the understanding of stress signaling in general and hypertonic stress signaling in particular in both yeast and higher eukaryotic models. The relationship between hyperosmotic stress signaling and the transcription and activation of immediate-early gene transcription factors is explored.