Hypertonicity activates GSK3β in tumor cells
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Responses to perturbations in the composition of the extracellular environment are crucial to maintain cell and tissue homeostasis. In hypertonic conditions cell lines derived from kidney epithelium initiate a variety of stress responses to maintain cell viability that include activation of Mitogen Activated Protein Kinases (MAPK). We previously showed that NaCl also regulates MAPK in different tumor cell lines and we now show that when hypertonic conditions induced with NaCl and other osmolytes were used to stimulate several tumor cell lines, Glycogen Synthase Kinase 3β (GSK3β) was rapidly dephosphorylated at serine 9 and its kinase activity was increased. This response was both time- and dose-dependent, it was independent of the Akt signaling pathway and did not increase steady state levels of phosphorylation of β-catenin, although the data suggested that activated GSK3β could regulate the activity of ERK1/2.
KeywordsGSK3β hypertonicity NaCl cell signaling
- 5.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 In pressGoogle Scholar
- 9.Roger F, Martin PY, Rousselot M, Favre H, Feraille E: Cell shrinkage triggers the activation of mitogen-activated protein kinases by hypertonicity in the rat kidney medullary thick ascending limb of the Henle's loop. Requirement of p38 kinase for the regulatory volume increase response. J Biol Chem 274: 34103–34110, 1999PubMedCrossRefGoogle Scholar
- 11.Li J, Yen C, Liaw D, Podsypanina K, Bose S, Wang SI, Puc J, Miliaresis C, Rodgers L, McCombie R, Bigner SH, Giovanella BC, Ittmann M, Tycko B, Hibshoosh H, Wigler MH, Parsons R: PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer. Science 275: 1943–1947, 1997PubMedCrossRefGoogle Scholar