GSK-3
Class of enzymes / From Wikipedia, the free encyclopedia
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Glycogen synthase kinase 3 (GSK-3) is a serine/threonine protein kinase that mediates the addition of phosphate molecules onto serine and threonine amino acid residues. First discovered in 1980 as a regulatory kinase for its namesake, glycogen synthase (GS),[2] GSK-3 has since been identified as a protein kinase for over 100 different proteins in a variety of different pathways.[3][4] In mammals, including humans, GSK-3 exists in two isozymes encoded by two homologous genes GSK-3α (GSK3A) and GSK-3β (GSK3B). GSK-3 has been the subject of much research since it has been implicated in a number of diseases, including type 2 diabetes, Alzheimer's disease, inflammation, cancer, addiction[5] and bipolar disorder.
glycogen synthase kinase 3 alpha | |||||||
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Identifiers | |||||||
Symbol | GSK3A | ||||||
NCBI gene | 2931 | ||||||
HGNC | 4616 | ||||||
OMIM | 606784 | ||||||
RefSeq | NM_019884 | ||||||
UniProt | P49840 | ||||||
Other data | |||||||
EC number | 2.7.11.26 | ||||||
Locus | Chr. 19 q13.2 | ||||||
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glycogen synthase kinase 3 beta | |||||||
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Identifiers | |||||||
Symbol | GSK3B | ||||||
NCBI gene | 2932 | ||||||
HGNC | 4617 | ||||||
OMIM | 605004 | ||||||
PDB | 1Q3W More structures | ||||||
RefSeq | NM_002093 | ||||||
UniProt | P49841 | ||||||
Other data | |||||||
EC number | 2.7.11.26 | ||||||
Locus | Chr. 3 q13.33 | ||||||
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GSK-3 is a serine/threonine protein kinase that phosphorylate either threonine or serine, and this phosphorylation controls a variety of biological activities, such as glycogen metabolism, cell signaling, cellular transport, and others.[6] GS inhibition by GSK-3β leads to a decrease in glycogen synthesis in the liver and muscles, along with increased blood glucose or hyperglycemia.[7] This is why GSK-3β is associated with the pathogenesis and progression of many diseases, such as diabetes, obesity, cancer,[8] and Alzheimer's disease.[9] It is active in resting cells and is inhibited by several hormones such as insulin, endothelial growth factor, and platelet-derived growth factor. Insulin indirectly inactivates GSK3 via downstream phosphorylation of the specific serine residues Ser21 and Ser9 in GSK-3 isoforms α and β, respectively via the PI3K/Akt pathway.[10][11]
As of 2019[update], GSK-3 is the only type of glycogen synthase kinase named and recognized. The gene symbols for GSK1 and GSK2 have been withdrawn by the HUGO Gene Nomenclature Committee (HGNC), and no new names for these "genes" nor their locations have been specified.[12][13]