Specific involvement of glycogen synthase kinase-3 in the function and activity of sex steroid hormone receptors reveals the complexity of their regulation

J Steroid Biochem Mol Biol. 2009 Nov;117(4-5):87-92. doi: 10.1016/j.jsbmb.2009.08.002. Epub 2009 Aug 22.

Abstract

Protein kinases represent key nodes for the integration of multiple intracellular signalling pathways, resulting in modulation of both ligand-dependent and ligand-independent mechanisms of sex steroid receptor (sSR) signalling cascades. The proline-directed Ser/Thr kinases including mitogen-activated protein kinases and cyclin dependent kinases were especially reported to contribute to the function and activity of sSRs. The relevant effects of these kinases are well-documented but the impact of glycogen synthase kinase-3 (GSK-3), another member of this kinase family, has been underestimated. Indeed, the specific role of GSK-3 regarding the different sSRs will help to understand further the complexity of sSR signalling. So far, AR and ERalpha were identified as GSK-3 substrates. Additionally, the docking properties of GSK-3 were demonstrated to play a crucial role in sSR signal transduction. Reciprocally, GSK-3 was described as a potential target of non-genomic effects of sSRs. Therefore, GSK-3 regulates and is regulated by sSRs. This review focuses on the emerging and promising involvements of GSK-3 regarding the signalling cascade of the respective sSRs. This review represents a necessary complement of information to highlight the importance of GSK-3 regarding sSR function and activity.

Publication types

  • Review

MeSH terms

  • Animals
  • Glycogen Synthase Kinase 3 / metabolism*
  • Humans
  • Phosphorylation
  • Receptors, Androgen / physiology*
  • Receptors, Estrogen / physiology*
  • Signal Transduction
  • Substrate Specificity

Substances

  • Receptors, Androgen
  • Receptors, Estrogen
  • Glycogen Synthase Kinase 3