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Literature summary for 2.7.11.26 extracted from

  • Buescher, J.L.; Phiel, C.J.
    A noncatalytic domain of glycogen synthase kinase-3 (GSK-3) is essential for activity (2010), J. Biol. Chem., 285, 7957-7963.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

Cloned (Comment) Organism
transient transfection of GST-tagged enzyme into HEK-293 cells coexpression with recombinant tau, coexpression of wild-type GSK-3alpha and wild-type GSK-3beta enhances Tau phosphorylation at Ser396 and Ser404 Homo sapiens

Protein Variants

Protein Variants Comment Organism
K148R site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type Homo sapiens
K85R site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type Homo sapiens
additional information deletion of the C-terminus to result in mutants alphaDELTACT1-4, with remaining 448, 441, 430, and 416 residues of 483, respectively, leads to loss of nearly all activity of the GSK-3 isoform and abolishes suppression of Wnt signaling Homo sapiens
additional information deletion of the C-terminus to result in mutants betaDELTACT1-4, with remaining 385, 378, 367, and 344 residues of 420, respectively, leads to loss of nearly all activity of the GSK-3 isoform and abolishes suppression of Wnt signaling Homo sapiens
P379A/P380A site-directed mutagenesis, the mutant shows rediuced activity compared to the wild-type Homo sapiens
P442A/P443A site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type Homo sapiens
R159A site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type Homo sapiens
R96A site-directed mutagenesis, the mutant activity is similar to the wild-type Homo sapiens
S9A site-directed mutagenesis, the mutant shows reduced activity compared to the wild-type Homo sapiens
T390A site-directed mutagenesis, the mutant activity is similar to the wild-type Homo sapiens
Y216F site-directed mutagenesis, the mutant activity is similar to the wild-type Homo sapiens
Y279F site-directed mutagenesis, the mutant activity is similar to the wild-type Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ required Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
ATP + [tau-protein] Homo sapiens
-
ADP + O-phospho-[tau-protein]
-
?

Organism

Organism UniProt Comment Textmining
Homo sapiens P49840 isozyme alpha
-
Homo sapiens P49841 isozyme beta
-

Purification (Commentary)

Purification (Comment) Organism
recombinant GST-tagged enzyme from HEK-293 cells by glutathione affinity chromatography Homo sapiens

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
ATP + [tau-protein]
-
Homo sapiens ADP + O-phospho-[tau-protein]
-
?
additional information GSK-3alpha-specific requirement for priming of tau protein Homo sapiens ?
-
?

Synonyms

Synonyms Comment Organism
glycogen synthase kinase-3
-
Homo sapiens
GSK-3
-
Homo sapiens
GSK-3alpha
-
Homo sapiens
GSK-3beta
-
Homo sapiens

Cofactor

Cofactor Comment Organism Structure
ATP
-
Homo sapiens

General Information

General Information Comment Organism
malfunction deletion of the C-terminus alphaDELTACT-4 leads to loss of nearly all activity of the GSK-3 isoform and abolishes suppression of Wnt signaling, GSK-3 C-terminal deletions mutants fail to interact with axin GID Homo sapiens
malfunction deletion of the C-terminus betaDELTACT-4 leads to loss of nearly all activity of the GSK-3 isoform and abolishes suppression of Wnt signaling, GSK-3 C-terminal deletions mutants fail to interact with axin GID Homo sapiens
additional information amino acids 345–367 of GSK-3beta are essential for enzyme activity with tau protein, structure-function analysis of GSK-3alpha and GSK-3beta in mammalian cells Homo sapiens
additional information amino acids 417-430 of GSK-3alpha are essential for enzyme activity with tau protein, structure-function analysis of GSK-3alpha and GSK-3beta in mammalian cells Homo sapiens
physiological function glycogen synthase kinase-3 (GSK-3) isoforms, GSK-3alpha and GSK-3beta, are serine/threonine kinases involved in numerous cellular processes and diverse diseases, including Alzheimer disease, cancer, and diabetes. GSK-3 isoforms function redundantly in some settings, while, in others, they exhibit distinct activities. In the canonical Wnt signaling pathway, GSK-3 phosphorylation of beta-catenin is regulated via interactions with the scaffold protein axin Homo sapiens
physiological function in the canonical Wnt signaling pathway, GSK-3 phosphorylation of beta-catenin is regulated via interactions with the scaffold protein axin. Glycogen synthase kinase-3 (GSK-3) isoforms, GSK-3alpha and GSK-3beta, are serine/threonine kinases involved in numerous cellular processes and diverse diseases, including Alzheimer disease, cancer, and diabetes. GSK-3 isoforms function redundantly in some settings, while, in others, they exhibit distinct activities. In the canonical Wnt signaling pathway, GSK-3 phosphorylation of beta-catenin is regulated via interactions with the scaffold protein axin Homo sapiens