Inhibitors | Comment | Organism | Structure |
---|---|---|---|
lithium | selective inhibition of GSK-3, blocks tau hyperphosphorylation either in cultured neurons or in rat brain | Rattus norvegicus | |
additional information | GSK-3 is inactivated by phosphorylation of serine 9 in GSK-3beta and serine 21 in GSK-3alpha subunits by mainly Akt. Hyperglycemia induces strong activity of GSK-3 in rat brain | Rattus norvegicus |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | required | Rattus norvegicus | |
additional information | no effect on enzyme activity with Na+ | Rattus norvegicus |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + [tau-protein] | Rattus norvegicus | phosphorylation of tau at various sites | ADP + O-phospho-[tau-protein] | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Rattus norvegicus | P18266 | - |
- |
Posttranslational Modification | Comment | Organism |
---|---|---|
phosphoprotein | GSK-3 is inactivated by phosphorylation of serine 9 in GSK-3beta and serine 21 in GSK-3alpha subunits. Akt appears to be the predominant kinase mediating this phosphorylation of GSK-3 | Rattus norvegicus |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
brain | - |
Rattus norvegicus | - |
hippocampus | - |
Rattus norvegicus | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
ATP + [tau-protein] | phosphorylation of tau at various sites | Rattus norvegicus | ADP + O-phospho-[tau-protein] | - |
? | |
ATP + [tau-protein] | phosphorylation at Ser198, Ser199, Ser202, Ser396, and Ser404 | Rattus norvegicus | ADP + O-phospho-[tau-protein] | - |
? |
Synonyms | Comment | Organism |
---|---|---|
glycogen synthase kinase-3 | - |
Rattus norvegicus |
GSK-3 | - |
Rattus norvegicus |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
30 | - |
assay at | Rattus norvegicus |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.4 | - |
assay at | Rattus norvegicus |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
ATP | - |
Rattus norvegicus |
General Information | Comment | Organism |
---|---|---|
physiological function | glycogen synthase kinase-3 plays an important role in the pathogenesis of Diabetes mellitus and Alzheimer's disease. Diabetic rats display an increased GSK-3 activity, and decreased activity and expression of Akt. And Abeta40 and Abeta42 are overproduced and the microtubule-associated protein tau is hyperphosphorylated in the hippocampus. Selective inhibition of GSK-3 attenuates the conditions of Abeta overproduction and tau hyperphosphorylation. GSK-3 regulates both the production of Amyloidbeta and the phosphorylation of tau in rat brain and may therefore contribute to Diabetes mellitus caused Alzheimer disease-like neurological defects. Hyperglycemia induces strong activity of GSK-3 and lowers activity of Akt in rat brain. The production of Abeta40 and Abeta42 is increased significantly while activation of GSK-3 and inhibition of Akt are induced in Diabetes mellitus | Rattus norvegicus |