title: Specific involvement of glycogen synthase kinase-3 in the function and activity of sex steroid hormone receptors reveals the complexity of their regulation.
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.
authors.affiliation: Hormones and Signal Transduction Group, German Cancer Research Center, DKFZ-ZMBH Alliance, Heidelberg, Germany.
authors.forename: Jean
authors.initials: J
authors.lastname: Grisouard
authors.forename: Doris
authors.initials: D
authors.lastname: Mayer
mesh_terms: D000818:Animals; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D011944:Receptors, Androgen / Q000502:physiology*; D011960:Receptors, Estrogen / Q000502:physiology*; D015398:Signal Transduction; D013379:Substrate Specificity
chemical_list: D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D038362:Glycogen Synthase Kinase 3