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Hypertonicity activates GSK3beta in tumor cells

Pablo Perez-Pinera1, Manuel Menendez-Gonzalez, Miguel del Valle

  • 1Departamento de Morfología y Biología Celular, Universidad de Oviedo, Oviedo, Spain. pab_correo@yahoo.com

Molecular and Cellular Biochemistry
|June 13, 2006
PubMed

Insights

Hypertonic stress deactivates Glycogen Synthase Kinase 3beta (GSK3beta) in tumor cells, increasing its activity. This response is independent of the Akt pathway and may regulate ERK1/2 signaling.

Area of Science:

  • Cellular Biology
  • Molecular Biology
  • Physiology

Background:

  • Cellular homeostasis relies on responses to extracellular environment changes.
  • Hypertonic conditions trigger stress responses, including Mitogen Activated Protein Kinases (MAPK) activation in kidney epithelium cells.
  • Previous work indicated NaCl regulates MAPK in tumor cell lines.

Purpose of the Study:

  • To investigate the effect of hypertonic conditions on Glycogen Synthase Kinase 3beta (GSK3beta) in tumor cell lines.
  • To determine the relationship between GSK3beta activity and other signaling pathways like Akt and ERK1/2 under hypertonic stress.

Main Methods:

  • Stimulation of various tumor cell lines with hypertonic conditions using NaCl and other osmolytes.
  • Analysis of GSK3beta phosphorylation at serine 9 and its kinase activity.
  • Investigation of the involvement of the Akt signaling pathway and beta-catenin phosphorylation.
  • Assessment of potential regulation of ERK1/2 activity by activated GSK3beta.

Main Results:

  • Hypertonic stress rapidly dephosphorylated GSK3beta at serine 9, increasing its kinase activity in tumor cell lines.
  • This GSK3beta response was time- and dose-dependent.
  • The observed GSK3beta activation was independent of the Akt signaling pathway and did not alter steady-state beta-catenin phosphorylation levels.
  • Data suggested activated GSK3beta could regulate ERK1/2 activity.

Conclusions:

  • Hypertonic stress induces a rapid and significant increase in GSK3beta kinase activity in tumor cells.
  • GSK3beta activation under hypertonic conditions is a distinct pathway, not directly involving Akt or beta-catenin.
  • Activated GSK3beta may play a role in regulating ERK1/2 signaling during cellular stress responses.

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