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Lithium inhibits glycogen synthase kinase-3 by competition for magnesium.

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 (Mg(2+)), 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 Mg(2+) concentration. We also found that GSK-3 is sensitive to chelation of free Mg(2+) by ATP and is progressively inhibited when ATP concentrations exceed that of Mg(2+). Given the cellular concentrations of ATP and Mg(2+), 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.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Ryves WJ,Harwood AJ

doi

10.1006/bbrc.2000.4169

subject

Has Abstract

pub_date

2001-01-26 00:00:00

pages

720-5

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(00)94169-X

journal_volume

280

pub_type

杂志文章

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