Glycogen synthase kinase-3 inhibition by lithium and beryllium suggests the presence of two magnesium binding sites
| Autor: | Rana Dajani, Adrian J. Harwood, Laurence H. Pearl, W. Jonathan Ryves |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Stereochemistry
Biophysics chemistry.chemical_element Biochemistry Binding Competitive Glycogen Synthase Kinase 3 Adenosine Triphosphate GSK-3 Humans Magnesium Binding site Enzyme Inhibitors Protein kinase A Glycogen synthase Molecular Biology Cyclin-dependent kinase 1 Binding Sites biology Dose-Response Relationship Drug Chemistry Glycogen Synthase Kinases Substrate (chemistry) Cell Biology Adenosine Diphosphate Kinetics Mitogen-activated protein kinase Calcium-Calmodulin-Dependent Protein Kinases biology.protein Beryllium Lithium Chloride |
| Zdroj: | Biochemical and biophysical research communications. 290(3) |
| ISSN: | 0006-291X |
| Popis: | Lithium inhibits (Li(+)) glycogen synthase kinase-3 (GSK-3) by competition for magnesium (Mg(2+)), but not ATP or substrate. Here, we show that the group II metal ion beryllium (Be(2+)) is a potent inhibitor of GSK-3 and competes for both Mg(2+) and ATP. Be(2+) also inhibits the related protein kinase cdc2 at similar potency, but not MAP kinase 2. To compare the actions of Li(+) and Be(2+) on GSK-3, we have devised a novel dual inhibition analysis. When Be(2+) and ADP are present together each interferes with the action of the other, indicating that both agents inhibit GSK-3 at the ATP binding site. In contrast, Li(+) exerts no interference with ADP inhibition or vice versa. We find, however, that Li(+) and Be(2+) do interfere with each other. These results suggest that Be(2+) competes for two distinct Mg(2+) binding sites: one is Li(+)-sensitive and the other, which is Li(+)-insensitive, binds the Mg:ATP complex. |
| Databáze: | OpenAIRE |
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