Ryves, William Jonathan and Harwood, Adrian J. 2001. Lithium Inhibits Glycogen Synthase Kinase-3 by Competition for Magnesium. Biochemical and Biophysical Research Communications 280 (3) , pp. 720-725. 10.1006/bbrc.2000.4169 |
Abstract
The mechanism by which lithium (Li+) inhibits the protein kinase glycogen synthase kinase-3 (GSK-3) is unknown. Here, we demonstrate that Li+ is a competitive inhibitor of GSK-3 with respect to magnesium (Mg2+), but not to substrate or ATP. This mode of inhibition is conserved between mammalian and Dictyostelium GSK-3 isoforms, and is not experienced with other group I metal ions. As a consequence, the potency of Li+ inhibition is dependent on Mg2+ concentration. We also found that GSK-3 is sensitive to chelation of free Mg2+ by ATP and is progressively inhibited when ATP concentrations exceed that of Mg2+. Given the cellular concentrations of ATP and Mg2+, our results indicate that Li+ will have a greater effect on GSK-3 activity in vivo than expected from in vitro studies and this may be a factor relevant to its use in the treatment of depression.
Item Type: | Article |
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Date Type: | Publication |
Status: | Published |
Schools: | Biosciences Neuroscience and Mental Health Research Institute (NMHRI) |
Subjects: | Q Science > Q Science (General) |
Publisher: | Elsevier |
ISSN: | 0006-291X |
Last Modified: | 19 Mar 2016 23:18 |
URI: | https://orca.cardiff.ac.uk/id/eprint/46399 |
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