Mitogen-activated protein kinase and its activator are regulated by hypertonic stress in Madin-Darby canine kidney cells

• Published in: The Journal of clinical investigation 1994-06, Vol.93 (6), p.2387-2392
• Main Authors: Itoh, T, Yamauchi, A, Miyai, A, Yokoyama, K, Kamada, T, Ueda, N, Fujiwara, Y
• Format: Article
• Language: English
• Subjects: Animals; Calcium-Calmodulin-Dependent Protein Kinases - metabolism; Cells, Cultured; Dogs; Enzyme Activation; Kidney - enzymology; Mitogen-Activated Protein Kinase Kinases; Osmolar Concentration; Protein Kinase C - physiology; Protein Kinases - metabolism
• ISSN: 0021-9738
• DOI: 10.1172/jci117245

Madin-Darby canine kidney cells behave like the renal medulla and accumulate small organic solutes (osmolytes) in a hypertonic environment. The accumulation of osmolytes is primarily dependent on changes in gene expression of enzymes that synthesize osmolytes (sorbitol) or transporters that uptake them (myo-inositol, betaine, and taurine). The mechanism by which hypertonicity increases the transcription of these genes, however, remains unclear. Recently, it has been reported that yeast mitogen-activated protein (MAP) kinase and its activator, MAP kinase-kinase, are involved in osmosensing signal transduction and that mutants in these kinases fail to accumulate glycerol, a yeast osmolyte. No information is available in mammals regarding the role of MAP kinase in the cellular response to hypertonicity. We have examined whether MAP kinase and MAP kinase-kinase are regulated by extracellular osmolarity in Madin-Darby canine kidney cells. Both kinases were activated by hypertonic stress in a time- and osmolarity-dependent manner and reached their maximal activity within 10 min. Additionally, it was suggested that MAP kinase was activated in a protein kinase C-dependent manner. These results indicate that MAP kinase and MAP kinase-kinase(s) are regulated by extracellular osmolarity.