Literature summary for 2.7.11.26 extracted from

Qu, Z.S.; Li, L.; Sun, X.J.; Zhao, Y.W.; Zhang, J.; Geng, Z.; Fu, J.L.; Ren, Q.G.
Glycogen synthase kinase-3 regulates production of amyloid-beta peptides and tau phosphorylation in diabetic rat brain (2014), ScientificWorldJournal, 2014, 878123.

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Inhibitors

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

Metals/Ions	Comment	Organism	Structure
Mg2+	required	Rattus norvegicus
additional information	no effect on enzyme activity with Na+	Rattus norvegicus

Natural Substrates/ Products (Substrates)

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

Organism	UniProt	Comment	Textmining
Rattus norvegicus	P18266	-	-

Posttranslational Modification

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

Source Tissue	Comment	Organism	Textmining
brain	-	Rattus norvegicus	-
hippocampus	-	Rattus norvegicus	-

Substrates and Products (Substrate)

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

Synonyms	Comment	Organism
glycogen synthase kinase-3	-	Rattus norvegicus
GSK-3	-	Rattus norvegicus

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
30	-	assay at	Rattus norvegicus

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
7.4	-	assay at	Rattus norvegicus

Cofactor

Cofactor	Comment	Organism	Structure
ATP	-	Rattus norvegicus

General Information

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

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Release 2023.1 (January 2023)