Perturbations of the extracellular ionic content by different hypo- or hyperosmolar stimuli initiate stress responses to maintain cell viability that include activation of Mitogen Activated Protein Kinases (MAPK) in cell lines derived from kidney epithelium. When hyperosmolar conditions induced by different salts occurred in the extracellular environment of tumor-derived cell lines, they activated the Extracellular Regulated Kinase 1/2 by increasing its phosphorylation steady-state on Thr202/Tyr204 in a time- and dose-dependent manner. It was found that Extracellular Regulated Kinase 1/2 activation is a consequence of selective phosphorylation by mitogen-activated protein kinase/ERK kinase. Changes in cell shape or in tubulin or actin cytoskeletal structure were not found, although cell growth arrest was observed as well as induction of apoptosis and modified cell migration ability that were dependent upon Extracellular Regulated Kinase 1/2 activation evidencing a critical role for the Extracellular Regulated Kinase 1/2 in mediating survival of cells in hyperosmotic conditions.
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Perez-Pinera P, Menendez-Gonzalez M, del Valle M, Vega JA. Sodium chloride regulates Extracellular Regulated Kinase 1/2 in different tumor cell lines. Mol Cell Biochem. 2006 Dec;293(1-2):93-101