Any feedback?
Literature summary for 2.7.11.26 extracted from
- Evidence that glycogen synthase kinase-3 isoforms have distinct substrate preference in the brain (2010), J. Neurochem., 115, 974-983.
Application
| Application | Comment | Organism |
|---|---|---|
| drug development | glycogen synthase kinase-3 activity and substrate phosphorylation, e.g. glycogen synthase, tau, CRMP2 and amyloid precursor protein, are reported to be abnormally high in both Type 2 diabetes and Alzheimer's disease. The enzyme GSK3 is a target for development of isozyme- and splice variant-selective inhibitors | Homo sapiens |
| drug development | glycogen synthase kinase-3 activity and substrate phosphorylation, e.g. glycogen synthase, tau, CRMP2 and amyloid precursor protein, are reported to be abnormally high in both Type 2 diabetes and Alzheimer's disease. The enzyme GSK3 is a target for development of isozyme-selective inhibitors | Homo sapiens |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| recombinant expression of GST-tagged GSK3beta1 and GSKbeta2 in HEK-293 cells, coepression with FLAG-tagged tau protein isoform 2 | Homo sapiens |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| additional information | overexpression of either GSK3beta isoform does not induce the phosphorylation of residues Ser199 and Ser404 | Homo sapiens |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| CT99021 | inhibition of GSK3 with CT99021 has little effect on the relative level of phosphorylation of Ser199 or Ser404 of human tau, but inhibition of GSK3beta using CT99021 results in dephosphorylation of endogenous c-Jun, Inh-2 and beta-catenin and dramatically increased c-Myc and beta-catenin expression | 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 | phoshorylation at residues Ser404, Ser199, Ser202 and Thr231 | ADP + O-phospho-[tau-protein] | - |
? | |
| additional information | Homo sapiens | glycogen synthase kinase-3 isoforms have distinct substrate preference in the brain, overview | ? | - |
? | |
| additional information | Homo sapiens | glycogen synthase kinase-3 isoforms have distinct substrate preference in the brain. There are GSK3 substrates with preference for GSK3beta1 over GSK3beta2, and others that hold no distinction, suggesting different modes of interaction with GSK3, overview | ? | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | P49840 | GSKalpha | - |
| Homo sapiens | P49841 | GSKbeta | - |
Purification (Commentary)
| Purification (Comment) | Organism |
|---|---|
| recombinant GST-tagged GSK3beta1 and GSKbeta2 from HEK-293 cells by glutathione affinity chromatography | Homo sapiens |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| brain | mammalian glycogen synthase kinase-3 (GSK3) is generated from two genes, GSK3alpha and GSK3beta, while a splice variant of GSK3beta (GSK3beta2), containing a 13 amino acid insert, is enriched in neurons | Homo sapiens | - |
| neuron | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| ATP + [tau-protein] | phoshorylation at residues Ser404, Ser199, Ser202 and Thr231 | Homo sapiens | ADP + O-phospho-[tau-protein] | - |
? | |
| additional information | glycogen synthase kinase-3 isoforms have distinct substrate preference in the brain, overview | Homo sapiens | ? | - |
? | |
| additional information | glycogen synthase kinase-3 isoforms have distinct substrate preference in the brain. There are GSK3 substrates with preference for GSK3beta1 over GSK3beta2, and others that hold no distinction, suggesting different modes of interaction with GSK3, overview | Homo sapiens | ? | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| glycogen synthase kinase-3 | - |
Homo sapiens |
| GSK3 | - |
Homo sapiens |
| GSK3A | - |
Homo sapiens |
| GSK3alpha | - |
Homo sapiens |
| GSK3B | - |
Homo sapiens |
| GSK3beta | - |
Homo sapiens |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| ATP | - |
Homo sapiens | |
| ATP | the ATP binding site of GSK3beta sits in the hydrophobic pocket between the two lobes, enclosed by a glycine rich loop (residues 60-70) and a hinge region (residues 134-139) while the substrate binding domain is within the C-terminal region | Homo sapiens | |
General Information
| General Information | Comment | Organism |
|---|---|---|
| malfunction | phosphorylation of CRMP2, CRMP4, beta-catenin, c-Myc, c-Jun and some residues on tau associated with Alzheimer's disease, is altered in cortical tissue lacking both isoforms of GSK3 | Homo sapiens |
| additional information | compared to GSK3beta1, the GSK3b2 isoform contains a 13 amino acid insert, which lies within the catalytic domain (between residues 303 and 304 of GSK3beta1), in a linker region flanked by a-helices (between domain X and XI) | Homo sapiens |
| physiological function | the enzyme phosphhorylates some residues on tau associated with Alzheimer's disease | Homo sapiens |
| physiological function | the enzyme phosphhorylates some residues on tau associated with Alzheimer's disease, phosphorylation of the microtubule associated protein tau. Inhibitor-2 phosphorylation is differentially regulated by GSK3beta1 and GSK3beta2, overview | Homo sapiens |
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
